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Enter author, analyte, or keyword to search publications.
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| NEW! Barrett, T.D., Palomino, H.L., Brondstetter, T.I., Kanelakis, K.C., Wu, X., Haug, P.V., Yan, W., Young, A., Hua, H., Hart, J.C., Tran, D.T., Venkatesan, H., Rosen, M.D., Peltier, H.M., Sepassi, K., Rizzolio, M.C., Bembenek, S.D., Mirzadegan, T., Rabinowitz, M.H., Shankley, N.P. (2011) Pharmacological characterization of 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), a potent and selective hypoxia-inducible factor prolyl hydroxylase inhibitor. Mol Pharmacol. Vol. 79(6):910-20.
HIF1a, HIF-1a, HIF1alpha, HIF-1a, HIF1a, hypoxia inducible factor-1, Johnson and Johnson
Analytes tested using MSD® assays: Erythropoietin, HIF-1alpha
Matrix tested: Cell culture supernatants
Summary: This study evaluated the therapeutic potential of a novel small molecule inhibitor of prolyl hydroxylase (PHD) enzyme in cell system, and in an inflammation-induced animal model.
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| NEW! Venkatesh, M., Wang, H., Cayer, J., Leroux, M., Salvail, D., Das, B., Wrobel, J.E., Mani, S. (2011) In Vivo and In Vitro Characterization of a First-in-Class Novel Azole Analog That Targets Pregnane X Receptor Activation. Mol Pharmacol. Vol. 80(1):124-35.
Nuclear receptor, Albert Einstein College of Medicine
Analytes tested using MSD assays: Phospho-ERK1/2, total ERK1/2
Matrix tested: LS174T cell lysates
Summary: This study evaluated the safety profile of a pregnane X receptor antagonist in vivo and in vitro in human and murine hepatocytes.
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| Ahad, A.M., Zuohe, S., Du-Cuny, L., Moses, S.A., Zhou, L.L., Zhang, S., Powis, G., Meuillet, E.J., Mash, E.A. (2011) Development of sulfonamide AKT PH domain inhibitors. Bioorg Med Chem. Vol. 19(6):2046-54. Epub 2011 Feb 1.
PI-3 Kinase, phospho/total Akt
Analytes tested using MSD assays: Phospho-(Ser473)/total Akt
Matrix tested: Human BxPC-3 pancreatic cancer cell lysates
Summary: This paper tested the effects of structural modification of sulfonamide Akt pleckstrin homology (PH) domain inhibitors on their activity.
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| Belibi, F., Zafar, I., Ravichandran, K., Bauer Segvic, A., Jani, A., Ljubanovic, D.G., Edelstein, C.L. (2011) Hypoxia-inducible factor 1{alpha} (HIF-1 {alpha}) and autophagy in polycystic kidney disease (PKD). Am J Physiol Renal Physiol. [Epub ahead of print].
LC3, Beclin-1, HIF-1a, HIF1a, HIF1alpha, hypoxia inducible factor 1 alpha, HIF1?, HIF-1?
Analytes tested using MSD assays: HIF-1alpha
Matrix tested: Mouse and rat kidney extracts
Summary: The aims of this study were to investigate the expression of HIF-1alpha in rat and mouse models of polycystic kidney disease and to determine whether markers of autophagy are elevated in these models.
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| Beltran, P.J., Chung, Y.A., Moody, G., Mitchell, P., Cajulis, E., Vonderfecht, S., Kendall, R., Radinsky, R., Calzone, F.J. (2011) Efficacy of Ganitumab (AMG 479), Alone and in Combination With Rapamycin, in Ewing's and Osteogenic Sarcoma Models. J Pharmacol Exp Ther. 2011 Mar 8. [Epub ahead of print].
IR, IGF1R, insulin-like growth factor type, insulin receptor substrate-1, Akt, PI3-Kinase, p70S6K, GSK3ß. GSK-3ß, GSK3b, GSK-3b, GSK3beta
Analytes tested using MSD assays: Phosphorylated and total Insulin receptor, p/t IGF1R, p/t IRS-1, p/t Akt, p/t p70S6K, p/t GSK-3beta
Matrix tested: Cell lysates
Summary: This study was based on the evaluation of an investigational antibody against human IGF1R in terms of its efficacy, either alone or in combination with rapamycin, against sarcoma xenografts.
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Dean, E.J., Cummings, J., Roulston, A., Berger, M., Ranson, M., Blackhall, F., Dive, C. (2011) Optimization of Circulating Biomarkers of Obatoclax-Induced Cell Death in Patients with Small Cell Lung Cancer. Neoplasia. Vol. 13(4): 339–347.
Analytes tested using MSD assays: Cleaved/Total Caspase 3
Matrix tested: Cell lysates
Summary: In this preclinical study, the combinatorial effect of Obatoclax (targets Bcl-2 family members) with platinum and etoposide chemotherapy was investigated in small cell lung cancer (SCLC) cell lines.
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| Dong, J., Sereno, A., Snyder, W.B., Miller, B.R., Tamraz, S., Doern, A., Favis, M., Wu, X., Tran, H., Langley, E., Joseph, I., Boccia, A., Kelly, R., Wortham, K., Wang, Q., Berquist, L., Huang, F., Gao, S.X., Zhang, Y., Lugovskoy, A., Martin, S., Gouvis, H., Berkowitz, S., Chiang, G., Reff, M., Glaser, S.M., Hariharan, K., Demarest, S.J. (2011) Stable IgG-like bispecific antibodies directed toward the type I insulin-like growth factor receptor demonstrate enhanced ligand blockade and anti-tumor activity. J Biol Chem. 2011 Feb 11;286(6):4703-17.
phosphatidylinositol 3 kinase, PI3K
Analytes tested using MSD assays: Phospho (Ser473) / total Akt
Matrix tested: Cell lysates
Summary: The aims of this study were to generate recombinant tetravalent bispecific antibodies against IGF-1R and to characterize them with regard to ligand blocking, inhibition of IGF-1R downstream signaling, and inhibition of tumor cell growth in vitro and in vivo.
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| Erlanson, D.A., Arndt, J.W., Cancilla, M.T., Cao, K., Elling, R.A., English, N., Friedman, J., Hansen, S.K., Hession, C., Joseph, I., Kumaravel, G., Lee, W.C., Lind, K.E., McDowell, R.S., Miatkowski, K., Nguyen, C., Nguyen, T.B., Park, S., Pathan, N., Penny, D.M., Romanowski, M.J., Scott, D., Silvian, L., Simmons, R.L., Tangonan, B.T., Yang, W., Sun, L. (2011) Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery. Bioorg Med Chem Lett. 2011 Mar 17.
p-Akt (Thr308)
Analytes tested using MSD assays: Phospho-Akt (Thr308)
Matrix tested: Cell lysates
Summary: In this paper, a modified method of fragment-based drug discovery technology called "Tethering with extenders" has been used to identify inhibitors of PDK1, a member of the PI3-Kinase pathway.
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| Fursov, N., Gates, I.V., Panavas, T., Giles-Komar, J., Powers, G. (2011) Development and Utilization of Activated STAT3 Detection Assays for Screening a Library of Secreted Proteins. Assay Drug Dev Technol. [Epub ahead of print].
Signal transducer and activator of transcription-3, transcription factor
Analytes tested using MSD assays: Phospho-STAT3 (Tyr705)
Matrix tested: Cell culture supernatants
Summary: In this study, the MSD platform was utilized to develop a high throughput method for screening a library of secreted proteins in order to identify inducers of STAT3 phosphorylation in a cell-based system. The authors noted that the MSD assay was robust, reliable, and highly suitable for high throughput application.
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| Gao, J., Chesebrough, J.W., Cartlidge, S.A., Ricketts, S.A., Incognito, L., Veldman-Jones, M., Blakey, D.C., Tabrizi, M., Jallal, B., Trail, P.A., Coats, S., Bosslet, K., Chang, Y.S. (2011) Dual IGF-I/II-Neutralizing Antibody MEDI-573 Potently Inhibits IGF Signaling and Tumor Growth. Cancer Res. 2011 Jan 18. [Epub ahead of print].
Insulin receptor, Insulin-like growth factor 1 receptor, IGF1R, IGF1-R, Insulin receptor substrate 1, PI3 Kinase, MedImmune, Astrazeneca
Analytes tested using MSD assays:
- Phosphorylated IR, IGF-1R, and IRS-1 (MSD Insulin Signaling Panel Phospho Protein Kit)
- Total IR, IGF-1R, and IRS-1 (Insulin Signaling Panel Total Protein Kit)
- Phosphorylated (Ser473) and total Akt (MSD Phospho (Ser473)/Total Akt Whole Cell Lysate Kit)
Matrix tested: Cell culture supernatants
Summary: This study evaluated the in vitro and in vivo effects of MEDI573, a fully human monoclonal antibody that binds to and neutralizes IGF-I and IGF-II, and inhibits IGF-induced signaling pathways. The therapeutic advantage of using MEDI573 as an anti-tumor drug was determined by receptor inhibition, tumor xenograft and cell growth inhibition studies.
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Gupte, J., Yang, L., Wu, X., Weiszmann, J., Hecht, R., Lemon, B., Lindberg, R., Wang, Z., Li, Y. (2011) The FGFR D3 Domain Determines Receptor Selectivity For Fibroblast Growth Factor 21. J Mol Biol. [Epub ahead of print].
Analytes tested using MSD assays: Phospho ERK1/2
Matrix tested: Cell lysates
Summary: The aim of this study was to elucidate the beta-Klotho-dependent signaling mechanism of fibroblast growth factor 21 (FGF21) by determining the domains of FGF21 that confer receptor-specificity, interaction, and activation.
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| Baima, E.T., Guzova, J.A., Mathialagan, S., Nagiec, E.E., Hardy, M.M., Song, L.R., Bonar, S.L., Weinberg, R.A., Selness, S.R., Woodard, S.S., Chrencik, J., Hood, W.F., Schindler, J.F., Kishore, N., Mbalaviele, G. (2010) Novel insights into the cellular mechanisms of the anti-inflammatory effects of NF-kB essential modulator (NEMO) binding domain peptides. J Biol Chem. Vol. 285(18):13498-506.
Interleukin, IL6, tumor necrosis factor, TNFa, TNF-a, TNFalpha, TNFa, TNF-a, nuclear factor kappa B, NF-kB, NFkappaB
Analytes tested using MSD assays: IL-6, TNF-alpha
Matrix tested: Human peripheral blood mononuclear cell (PBMC) supernatants
Summary: In this study, the binding interactions of different components of the IkB kinase (IKK) complex have been examined and peptides to inhibit this binding have been assessed in order to disrupt the IKK complex. IKK complex consists of IKK-1, IKK-2 and NEMO (NF-kB essential modulator).
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| Carnahan, J., Beltran, P.J., Babij, C., Le, Q., Rose, M.J., Vonderfecht, S., Kim, J.L., Smith, A.L., Nagapudi, K., Broome, M.A., Fernando, M., Kha, H., Belmontes, B., Radinsky, R., Kendall, R., Burgess, T.L. (2010) Selective and potent raf inhibitors paradoxically stimulate normal cell proliferation and tumor growth. Mol Cancer Ther. Vol. 9(8):2399-410.
MAP Kinase
Analytes tested using MSD assays: Phosphorylated ERK, total ERK
Matrix tested: Tumor xenograft lysates
Summary: In this study, a series of Raf inhibitors were examined for their in vitro and in vivo activities across cell lines and tumor xenografts harboring mutant B-Raf, a potent activator of the MAPK pathway.
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| Dean, E.J., Ward, T., Pinilla, C., Houghten, R., Welsh, K., Makin, G., Ranson, M., Dive, C. (2010) A small molecule inhibitor of XIAP induces apoptosis and synergizes with vinorelbine and cisplatin in NSCLC. Br J Cancer. Vol. 102(1):97-103.
XIAP, apoptosis, malignant, tumor
Analytes tested using MSD assays: Cleaved Caspase-3 / Total Caspase-3
Matrix tested: Human non-small cell lung cancer (NSCLC) cell lysates
Summary: This study investigated a phenylurea-based small molecule inhibitor of XIAP (X-linked IAP), which is an inhibitor of apoptosis and is over-expressed in malignant cells.
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| Edgar, K.A., Wallin, J.J., Berry, M., Lee, L.B., Prior, W.W., Sampath, D., Friedman, L.S., Belvin, M. (2010) Isoform-specific phosphoinositide 3-kinase inhibitors exert distinct effects in solid tumors. Cancer Res. Vol. 70(3):1164-72.
PI3Kinase, PI3K
Analytes tested using MSD assays: Phospho Akt (Ser473), Phospho S6 (Ser235/236)
Matrix tested: Tumor xenograft lysates
Summary: In this study, the effects of PI3 Kinase isoform-selective inhibitors were examined in cancer cells.
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Fosgerau, K., Galle, P., Hansen, T., Albrechtsen, A., Rieper Cde, L., Pedersen, B.K., Larsen, L.K., Thomsen, A.R., Pedersen, O., Hansen, M.B., Steensberg, A. (2010) Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes. J Endocrinol. Vol. 204(3):265-73.
Analytes tested using MSD assays: Phospho-Akt, total Akt, phosho-IRS-1, total IRS-1, phospho-IR, total IR
Matrix tested: Mouse liver and muscle tissue lysates
Summary: This study investigated a possible causative role of IL-6 auto-antibodies in the pathogenesis of type 2 diabetes and hyperglycemia by inducing different levels of circulating auto-antibodies to IL6 in mice and testing for metabolic implications.
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| Grimshaw, K.M., Hunter, L.J., Yap, T.A., Heaton, S.P., Walton, M.I., Woodhead, S.J., Fazal, L., Reule, M., Davies, T.G., Seavers, L.C., Lock, V., Lyons, J.F., Thompson, N.T., Workman, P., Garrett, M.D. (2010) AT7867 is a potent and oral inhibitor of AKT and p70 S6 kinase that induces pharmacodynamic changes and inhibits human tumor xenograft growth. Mol Cancer Ther. Vol. 9(5):1100-10.
fragment-based lead discovery, PI3 kinase
Analytes tested using MSD assays: Phospho Akt (Ser473)/total Akt, Phospho GSK-3beta (Ser9) / total GSK-3beta, Phospho S6 ribosomal protein (Ser235/Ser236), total S6 ribosomal protein (S6RP)
Matrix tested: U87MG glioblastoma cell lysates
Summary: In this study, the pharmacologic profile of a potent, small molecule inhibitor (AT7867) of AKT has been examined in detail. This agent has been demonstrated to cause appropriate biomarker modulation and apoptosis in vitro and in vivo and exhibit antitumor efficacy in tumor xenografts.
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| Harikumar, K.B., Kunnumakkara, A.B., Ochi, N., Tong, Z., Deorukhkar, A., Sung, B., Kelland, L., Jamieson, S., Sutherland, R., Raynham, T., Charles, M., Bagherazadeh, A., Foxton, C., Boakes, A., Farooq, M., Maru, D., Diagaradjane, P., Matsuo, Y., Sinnett-Smith, J., Gelovani, J., Krishnan, S., Aggarwal, B.B., Rozengurt, E., Ireson, C.R., Guha, S. (2010) A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. Vol. 9(5):1136-46.
PI3Kinase, PI3K
Analytes tested using MSD assays: Cleaved caspase 3
Matrix tested: Cell culture supernatants
Summary: This study examined the in vitro and in vivo effects of a small molecule Protein Kinase D specific inhibitor, CRT0066101, in pancreatic cancer.
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| Hatzivassiliou, G., Song, K., Yen, I., Brandhuber, B.J., Anderson, D.J., Alvarado, R., Ludlam, M.J., Stokoe, D., Gloor, S.L., Vigers, G., Morales, T., Aliagas, I., Liu, B., Sideris, S., Hoeflich, K.P., Jaiswal, B.S., Seshagiri, S., Koeppen, H., Belvin, M., Friedman, L.S., Malek, S. (2010) RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature. Vol. 464(7287):431-5.
RAF, RAS, KRAS, BRAF, RAF-MEK-ERK pathway
Analytes tested using MSD assays: Phospho (Ser 217/ 221) / Total MEK1/2
Matrix tested: Tumor cell lysates
Summary: This paper examined the different mechanisms of action of small molecule ATP-competitive RAF kinase inhibitors in context of the RAS-RAF-MEK-ERK signaling pathway.
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Hendriks, B.S., Seidl, K.M., Chabot, J.R. (2010) Two additive mechanisms impair the differentiation of 'substrate-selective' p38 inhibitors from classical p38 inhibitors in vitro. BMC Systems Biology. Vol. 4:23.
Analytes tested using MSD assays: User developed assay for phospho ATF2 and phospho MK-2
Matrix tested: Cell lysates
Summary: This study investigated the mechanism of action of a 'substrate-selective' p38 inhibitor that is able to preferentially block the activity of p38 against one substrate (MK2) versus another (ATF2).
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| Hirai, H., Sootome, H., Nakatsuru, Y., Miyama, K., Taguchi, S., Tsujioka, K., Ueno, Y., Hatch, H., Majumder, P.K., Pan, B.S., Kotani, H. (2010) MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Ther. Vol. 9(7):1956-67.
phosphatidylinositol 3 kinase, PI3K
Analytes tested using MSD assays: Phospho (Ser473) / total Akt
Matrix tested: Cell culture supernatants
Summary: This paper discusses the combination effects of MK-2206, an orally active allosteric Akt inhibitor, with various anticancer drugs.
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| Hua, F., Henstock, P.V., Tang, B. (2010) ERK activation by GM-CSF reduces effectiveness of p38 inhibitor on inhibiting TNFalpha release. Int Immunopharmacol. 2010 Apr 14. [Epub ahead of print].
tumor necrosis factor, TNFalpha, TNF-a, TNFa, TNF-a, TNFa, Jun N-terminal kinases, heat shock protein, retinoblastoma
Analytes tested using MSD assays: TNF-alpha, phospho ERK, phospho p38, phospho JNK, phospho HSP27 (Ser 78), phospho Rb (Ser780)
Matrix tested: Peripheral blood mononuclear cell (PBMC) culture supernatants
Summary: This study evaluated how different cytokine environments affect the potency of a p38 inhibitor. Different stimulation conditions involving LPS and cytokines were tested.
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| Manley, P.W., Stiefl, N., Cowan-Jacob, S.W., Kaufman, S., Mestan, J., Wartmann, M., Wiesmann, M., Woodman, R., Gallagher, N. (2010) Structural resemblances and comparisons of the relative pharmacological properties of imatinib and nilotinib. Bioorg Med Chem. Vol. 18(19):6977-86. Epub 2010 Aug 14.
Imatinib, Nilotinib, BCR-ABL1
Analytes tested using MSD assays: Colony-stimulating Factor-1 Receptor (CSF-1R)
Matrix tested: HEK293H cell lysates
Summary: The focus of this study was to assess the similarity between two tyrosine kinase inhibitors developed for the treatment of chronic myelogenous leukaemia (CML) in terms of structural and molecular poperties using a range of algorithms.
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| Mnich, S.J., Blanner, P.M., Hu, G., Shaffer, A.F., Happa, F.A., O'Neil, S., Ukairo, O., Weiss, D., Welsh, E., Storer, C., Mbalaviele, G., Ichijo, H., Monahan, J.B., Hardy, M.M., Eda, H. (2010) Critical role for apoptosis signal-regulating kinase 1 in the development of inflammatory K/BxN serum-induced arthritis. Int Immunopharmacol. [Epub ahead of print].
Interleukin, IL-1ß, IL1ß, IL1b, IL-1b, IL1beta, monocyte chemotactic protein-1, CCL2, IL6, tumor necrosis factor, TNFalpha, TNF-a, TNFa, TNF-a, TNFa
Analytes tested using MSD assays: IL-1beta, IL-6, KC/GRO, MCP-1, TNF-alpha
Matrix tested: Mouse plasma, cell culture supernatants
Summary: This study tested the role of apoptosis signal-regulating kinase-1 (ASK-1) in a mouse model of rheumatoid arthritis and indicated that ASK1 is involved in the production of proinflammatory mediators in response to TNF-alpha stimulation in the arthritic joint.
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Paoloni, M.C., Mazcko, C., Fox, E., Fan, T., Lana, S., Kisseberth, W., Vail, D.M., Nuckolls, K., Osborne, T., Yalkowsy, S., Gustafson, D., Yu, Y., Cao, L., Khan, C. (2010) Rapamycin Pharmacokinetic and Pharmacodynamic Relationships in Osteosarcoma: A Comparative Oncology Study in Dogs. PLoS One. Vol. 5(6): e11013.
Analytes tested using MSD assays: Phospho (Ser473) / total Akt, phospho (Ser240/244) / total S6RP
Matrix tested: Tumor biopsy lysates, PBMC lysates
Summary: The focus of this study was to identify a safe, pharmacokinetically and pharmacodynamically relevant dose of rapamycin (mTOR inhibitor) in tumor bearing dogs, in order to include the dog in future drug development and clinical studies.
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| Putcha, P., Danzer, K.M., Kranich, L.R., Scott, A., Silinski, M., Mabbett, S., Hicks, C.D., Veal, J.M., Steed, P.M., Hyman, B.T., McLean, P.J. (2010) Brain-permeable small-molecule inhibitors of Hsp90 prevent alpha-synuclein oligomer formation and rescue alpha-synuclein-induced toxicity. J Pharmacol Exp Ther. Vol. 332(3):849-57.
Parkinson's Disease, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Lewy Body, heat shock protein
Analytes tested using MSD assays: Total HSP70
Matrix tested: Sprague-Dawley rat brain lysates
Summary: In this paper, a group of synthetic, orally active, small molecule Hsp90 inhibitor compounds were screened in an in vitro model of alpha synuclein oligomerization and toxicity.
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| Rajagopalan, L.E., Davies, M.S., Kahn, L.E., Kornmeier, C.M., Shimada, H., Steiner, T.A., Zweifel, B.S., Wendling, J.M., Payne, M.A., Loeffler, R.F., Case, B.L., Norton, M.B., Parikh, M.D., Nemirovskiy, O.V., Mourey, R.J., Masferrer, J.L., Misko, T.P., Kolodziej, S.A. (2010) Biochemical, cellular, and anti-inflammatory properties of a potent, selective, orally bioavailable benzamide inhibitor of Rho kinase activity. J Pharmacol Exp Ther. Vol. 333(3):707-16.
Interleukin, IL8, monocyte chemotactic protein 1, Rho kinase
Analytes tested using MSD assays: IL-8, MCP-1
Matrix tested: Cell culture supernatants
Summary: The aim of this study was to characterize a novel, potent, orally bioavailable Rho kinase inhibitor and validate the role of this enzyme in lymphocyte and neutrophil activation and migration and in the endothelial cell-mediated synthesis of chemokines and adhesion molecules.
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| Roubert, P., Dubern, B., Plas, P., Lubrano-Berthelier, C., Alihi, R., Auger, F., Deoliveira, D.B., Dong, J.Z., Basdevant, A., Thurieau, C., Clement, K. (2010) Novel pharmacological MC4R agonists can efficiently activate mutated-MC4R from obese patients with impaired endogenous agonist response. J Endocrinol. [Epub ahead of print].
obesity, cAMP, melanocortins
Analytes tested using MSD assays: Cyclic AMP
Matrix tested: Cell culture supernatants
Summary: In this study, the in vitro effects of two novel melanocortin agonists were tested on a set of human melanocortin 4 receptor (MC4R) mutations. MC4R plays a predominant role in body weight regulation and mutations in this gene are responsible for the most common genetic cause of human obesity.
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| Shimada, H., Rajagopalan, L.E. (2010) Rho-kinase mediates lysophosphatidic acid-induced IL-8 and MCP-1 production via p38 and JNK pathways in human endothelial cells. FEBS Lett. Vol. 584(13):2827-32.
Interleukin, IL8, monocyte chemotactic protein 1, Lysophosphatidic acid, Rho kinase
Analytes tested using MSD assays: IL-8, MCP-1
Matrix tested: Cell culture supernatants
Summary: The aim of this study was to investigate the signal transduction promoted by Lysophosphatidic acid (LPA), which is a proinflammatory mediator eminent in several diseases.
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| Skepner, J.E., Shelley, L.D., Ji, C., Reidich, B., Luo, Y. (2010) Chronic treatment with epoxyeicosatrienoic acids modulates insulin signaling and prevents insulin resistance in hepatocytes. Prostaglandins &Other Lipid Mediators. [Article in press].
Insulin resistance, Epoxyeicosatrienoic acids, PI3K, PI3-kinase
Analytes tested using MSD assays: Phospho (Ser473) / total Akt assay (duplex kit), Phospho (Thr183/Tyr185) / total JNK assay (duplex kit), Phospho IRS-1(Ser312) assay (singleplex kit), Insulin signaling panel (total protein assay) (triplex kit)
Matrix tested: HepG2 cell lysates
Summary: This study investigated whether epoxyeicosatrienoic acids (EETs) that are produced by metabolism of arachidonic acid by cytochrome P450 epoxygenases, regulate insulin signal transduction pathway and gluconeogenesis in cultured hepatocytes.
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| Sutherlin, D.P., Sampath, D., Berry, M., Castanedo, G., Chang, Z., Chuckowree, I., Dotson, J., Folkes, A., Friedman, L., Goldsmith, R., Heffron, T., Lee, L., Lesnick, J., Lewis, C., Mathieu, S., Nonomiya, J., Olivero, A., Pang, J., Prior, W.W., Salphati, L., Sideris, S., Tian, Q., Tsui, V., Wan, N.C., Wang, S., Wiesmann, C., Wong, S., Zhu, B.Y. (2010) Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the treatment of cancer. J Med Chem. Vol. 53(3):1086-97.
PI3K, Akt, mTOR, xenograft model, breast cancer
Analytes tested using MSD assays: Phospho Akt (Ser473), Total Akt, Phospho S6RP (Ser235/236), Total S6RP
Matrix tested: MCF7.1 tumor cell lysates
Summary: This study focused on the identification of novel PI3 Kinase inhibitors that are structurally diverse and that have varying activity towards mTOR.
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| Yang, N.Y., Fernandez, C., Richter, M., Xiao, Z., Valencia, F., Tice, D.A., Pasquale, E.B. (2010) Crosstalk of the EphA2 receptor with a serine/threonine phosphatase suppresses the Akt-mTORC1 pathway in cancer cells. Cell Signal. 2010 Sep 15. [Epub ahead of print].
Ephrin, Tumor suppression, Prostate cancer
Analytes tested using MSD assays: Phospho Akt (Ser473)
Matrix tested: Cell lysates
Summary: The aim of this study was to elucidate the signaling mechanism involved in the suppression of Akt-mTORC1 oncogenic pathway by EphA2 receptor.
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| Avondoglio, D., Scott, T., Kil, W.J., Sproull, M., Tofilon, P.J., Camphausen, K. (2009) High throughput evaluation of gamma-H2AX. Radiation Oncology. Vol. 4:31.
Histone H2AX, DNS, Double stranded break, radiation
Analytes tested using MSD assays: Gamma-H2AX
Matrix tested: Cell and xenograft tumor lysates
Summary: This study is based on the development of an MSD assay to measure gamma-H2AX as a marker of double stranded DNA breaks induced by radiation therapy.
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Beltran, P.J., Mitchell, P., Chung, Y.A., Cajulis, E., Lu, J., Belmontes, B., Ho, J., Tsai, M.M., Zhu, M., Vonderfecht, S., Baserga, R., Kendall, R., Radinsky, R., Calzone, F.J. (2009) AMG 479, a fully human anti-insulin-like growth factor receptor type I monoclonal antibody, inhibits the growth and survival of pancreatic carcinoma cells. Mol Cancer Ther. Apr 14. [Epub ahead of print].
Analytes tested using MSD assays: Total and phosphorylated IGF-IR, Insulin receptor (IR), and Akt
Matrix tested: BxPC-3 and MiaPaCa2 (pancreatic carcinoma cell lines) xenograft tumor lysates
Summary: In this study, the therapeutic potential of AMG 479, a fully human monoclonal antibody against insulin-like growth factor (IGF) type I receptor (IGF-IR), was evaluated in pancreatic carcinoma cell lines.
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| Curtis, A.M., Wilkinson, P.F., Gui, M., Gales, T.L, Hu, E., Edelberg, J.M. (2009) p38 mitogen-activated protein kinase targets the production of proinflammatory endothelial microparticles. J Thromb Haemost. Vol. 7(4):701-9.
Inflammation, MAPK signaling, Endothelial dysfunction
Analytes tested using MSD assays: Total p38, Phosphorylated p38
Matrix tested: Human airway epithelial cell (HAEC) lysates
Summary: In this paper, the role of p38 MAPK signaling in the formation and function of endothelial microparticles has been investigated.
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| Dakappagari, N., Neely, L., Tangri, S., Lundgren, K., Hipolito, L., Estrellado, A., Burrows, F., Zhang, H. (2009) An investigation into the potential use of serum Hsp70 as a novel tumour biomarker for Hsp90 inhibitors. Biomarkers. Vol. 15(1):31-8.
HSP70, HSP-70, HSP90, HSP-90, cancer
Analytes tested using MSD assays: HSP70
Matrix tested: Human serum, cell lysates
Summary: This study is based on the development of a highly sensitive MSD assay for the quantification of secreted and intracellular Hsp70 induced by HSP90 inhibitors in small cell lung cancer (SCLC) cell lines.
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| Engstrom, L., Pinzon-Ortiz, M.C., Li, Y., Chen, S.C., Kinsley, D., Nelissen, R., Fine, J.S., Mihara, K., Manfra, D. (2009) Characterization of a murine keyhole limpet hemocyanin (KLH)-delayed-type hypersensitivity (DTH) model: role for p38 kinase. Int Immunopharmacol. Vol. 9(10):1218-27.
tumor necrosis factor, TNFa, TNF-a, TNF-a, TNFa, TNFalpha
Analytes tested using MSD assays: TNF-alpha, phosphorylated and total p38, phosphorylated and total JNK, phosphorylated and total ERK
Matrix tested: Mouse ear whole organ cultures, ear lysates, lymph node lysates
Summary: The focus of this study was to characterize the delayed type hypersensitivity response induced by KLH at a cellular and molecular level, and use this model to evaluate the effects of an immunomodulator, BIRB-796.
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| Guillard, S., Clarke, P.A., Te Poele, R., Mohri, Z., Bjerke, L., Valenti, M., Raynaud, F., Eccles, S.A., Workman, P. (2009) Molecular pharmacology of phosphatidylinositol 3-kinase inhibition in human glioma. Cell Cycle. Vol. 8(3):443-53.
PI-103, glioma, PI3 kinase, mTOR, cell cycle, cytostasis
Analytes tested using MSD assays:
1) Phospho Akt (Thr308) (singleplex plate)
2) Phospho Akt (Ser473), phospho GSK-3beta (Ser9), phospho p70S6K (Thr421/Ser424) (triplex plate)
3) Total Akt, GSK-3beta, p70S6K (triplex plate)
4) Phospho S6 ribosomal protein (Ser235/Ser236), total S6 ribosomal protein (S6RP; duplex plate)
Matrix tested: U87 and SF268 human glioma cell lysates
Summary: In this study, the molecular mechanism of action of a PI3-kinase and mTOR inhibitor was examined in human glioma cell lines.
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| Hasumi, Y., Baba, M., Ajima, R., Hasumi, H., Valera, V.A., Klein, M.E., Haines, D.C., Merino, M.J., Hong, S.B., Yamaguchi, T.P., Schmidt, L.S., Linehan, W.M. (2009) Homozygous loss of BHD causes early embryonic lethality and kidney tumor development with activation of mTORC1 and mTORC2. Proc Natl Acad Sci U S A. Vol. 106(44):18722-7.
Hamartoma syndrome, Birt Hogg Dube
Analytes tested using MSD assays: Phospho Akt (Ser473), Phospho S6K (Thr421/Ser424), Phospho S6R (Ser240/244)
Matrix tested: Human kidney tumor cell lysates
Summary: In this study, the phenotype of an embryonic lethal BHD homozygous knockout mouse model has been analyzed and the kidney tumors that develop in a BHD heterozygous knockout mouse model have been characterized in comparison to human BHD kidney tumors. BHD is a tumor suppressor gene, and mutations in this gene predispose patients to develop renal tumors.
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| Huang, S.A., Hancock, M.K., Pitman, J.L., Orth, A.P., Gekakis, N. (2009) Negative Regulators of Insulin Signaling Revealed in a Genome-Wide Functional Screen. PLoS One. Vol. 4(9):e6871.
Type 2 Diabetes, insulin resistance, Akt, FOXO1A
Analytes tested using MSD assays: Phospho (Ser 473) and total Akt
Matrix tested: COS7 cell lysates
Summary: This paper is based on a cDNA screen for negative regulators of Insulin which are of therapeutic interest with respect to Type 2 Diabetes.
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| Jaulmes, A., Sansilvestri-Morel, P., Rolland-Valognes, G., Bernhardt, F., Gaertner, R., Lockhart, B.P., Cordi, A., Wierzbicki, M., Rupin, A., Verbeuren, T.J. (2009) Nox4 mediates the expression of plasminogen activator inhibitor-1 via p38 MAPK pathway in cultured human endothelial cells. Thromb Res. Vol. 124(4):439-46.
Endothelial cells, NADPH oxidase, PAI-1, siRNA, Human Umbilical Venous Endothelial Cells
Analytes tested using MSD assays: Phospho MAPKAPK2 (Thr334), Phospho NF-kB (Ser468), Phospho (Ser217/221) / total MEK 1/2
Matrix tested: HUVEC cell lysates
Summary: This study tested the hypothesis that NADPH oxidase is responsible for the expression and activity of Plasminogen Activator Inhibitor 1, which is an inhibitor of fibrinolysis associated with myocardial infarction and metabolic syndrome.
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| Koppe, S.W., Elias, M., Moseley, R.H., Green, R.M. (2009) Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet. Am J Physiol Gastrointest Liver Physiol. Vol. 297(2):G378-84.
Interleukin, IL1beta, IL-1b, IL1b, IL-1ß, IL1ß, elaidic acid, nonalcoholic fatty liver disease, insulin-sensitivity, trans fat
Analytes tested using MSD assays: Insulin, leptin, IL-1beta
Matrix tested: Mouse serum and liver homogenates
Summary: In this study, the authors investigated the effect of trans facts on the development of nonalcoholic fatty liver disease by comparing the effect of a murine diet high in trans fat to a standard high-fat diet that is devoid of trans fats but high in saturated fats.
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| Ma, Q., Cavallin, L.E., Yan, B., Zhu, S., Duran, E.M., Wang, H., Hale, L.P., Dong, C., Cesarman, E., Mesri, E.A., Goldschmidt-Clermont, P.J. (2009) Antitumorigenesis of antioxidants in a transgenic Rac1 model of Kaposi's sarcoma. Proc Natl Acad Sci U S A. Vol. 106(21):8683-8.
angiogenesis, hypoxia-inducible factor 1 alpha, reactive oxygen species (ROS), tumorigenesis
Analytes tested using MSD assays: Phospho Akt (Ser 473)
Matrix tested: Mouse tumor tissue homogenates
Summary: This paper tested the effects of constitutive expression of Rac1, which is an inflammatory signaling mediator triggering reactive oxygen species (ROS) production. It demonstrated that expression of a constitutively active Rac1 produces Kaposi's sarcoma like tumors in transgenic mice through mechanisms involving ROS-driven proliferation, up-regulation of AKT signaling, and hypoxia inducible factor 1-alpha related angiogenesis.
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Nicklin, P., Bergman, P., Zhang, B., Triantafellow, E., Wang, H., Nyfeler, B., Yang, H., Hild, M., Kung, C., Wilson, C., Myer, V.E., MacKeigan, J.P., Porter, J.A., Wang, Y.K., Cantley, L.C., Finan, P.M., Murphy, L.O. (2009) Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. Vol. 136(3):521-34.
Analytes tested using MSD assays: Phospho S6K1 (Thr389)
Matrix tested: HeLa cell extracts
Summary: The focus of this paper was to identify the mechanism by which L-glutamine exerts control over mTOR signaling.
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| Raynaud, F.I., Eccles, S.A., Patel, S., Alix, S., Box, G., Chuckowree, I., Folkes, A., Gowan, S., De Haven Brandon, A., Di Stefano, F., Hayes, A., Henley, A.T., Lensun, L., Pergl-Wilson, G., Robson, A., Saghir, N., Zhyvoloup, A., McDonald, E., Sheldrake, P., Shuttleworth, S., Valenti, M., Wan, N.C., Clarke, P.A., Workman, P. (2009) Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ther. Vol. 8(7):1725-1738.
PI3K, clinical trial
Analytes tested using MSD assays:
1) Phospho Akt (Ser473) / total Akt (duplex plate)
2) Phospho Akt (Thr308) (singleplex plate)
3) Phospho Akt (Ser473), phospho GSK-3beta (Ser9), phospho p70S6K (Thr421/Ser424) (triplex plate)
4) Total Akt, GSK-3beta, p70S6K (triplex plate)
5) Phospho S6 ribosomal protein (Ser235/Ser236), total S6 ribosomal protein (S6RP; duplex plate)
Matrix tested: Tumor cell lysate U87MG, Tumor xenograft lysate
Summary: This paper examined the properties of pharmaceutically optimized phosphatidylinositide 3-kinase inhibitors in glioblastoma cell line.
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| Rogers, S.J., Box, C., Chambers, P., Barbachano, Y., Nutting, C.M., Rhys-Evans, P., Workman, P., Harrington, K.J., Eccles, S.A. (2009) Determinants of response to epidermal growth factor receptor tyrosine kinase inhibition in squamous cell carcinoma of the head and neck. J Pathol. Vol. 218(1):122-30.
epidermal growth factor receptor, squamous cell carcinoma of the head and neck, E-cadherin, western blot, flow cytometry, immunoassay; tyrosine kinase
Analytes tested using MSD assays: Phospho (Tyr1173) and total EGFR Duplex, phospho (Tyr1248) ERB-B2 and total ERB-B2, MET
Matrix tested: Tumor xenograft lysates
Summary: This study was designed to address the correlation between the expression and phosphorylation levels of some biomarkers such as EGFR, MET, and BRK and the susceptibility to inhibition by Gefitinib (an EGFR tyrosine kinase inhibitor) in cell lines derived from tumors. MSD data was compared to Flow Cytometry results for validation of MSD technology and good correlation was observed for all targets tested in the paper.
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| Sari, Y., Chiba, T., Yamada, M., Rebec, G.V., Aiso, S. (2009) A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: Signaling pathway investigations. Neuroscience. Vol. 164(4):1653-64.
Type 2 Diabetes, insulin resistance, Akt, FOXO1A
Analytes tested using MSD assays: Phospho (Ser 112) and total BAD, phospho p38
Matrix tested: Mouse brain lysates
Summary: In this study, the mechanisms underlying the neuroprotective effects of colivelin (CLN), a novel peptide, were examined in a mouse model of fetal alcohol exposure.
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Shah, M., Stebbins, J.L., Dewing, A., Qi, J., Pellecchia, M., Ronai, Z.A. (2009) Inhibition of Siah2 ubiquitin ligase by vitamin K3 (menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis. Epub 2009 Aug 27.
Analytes tested using MSD assays: E3 ubiquitin ligase activity
Matrix tested: Assay buffer
Summary: In this study, the MSD platform was utilized for establishing a high-throughput screening method to identify inhibitors of Siah2 ubiquitin ligase activity.
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| Singh, D., Smyth, L., Borrill, Z., Sweeney, L., Tal-Singer, R. (2009) A Randomized, Placebo-Controlled Study of the Effects of the p38 MAPK Inhibitor SB-681323 on Blood Biomarkers of Inflammation in COPD Patients. J Clin Pharmacol. Vol. 50(1):94-100.
Chronic obstructive pulmonary disease, COPD, corticosteroids, heat shock protein
Analytes tested using MSD assays: Phospho (Ser15) HSP27
Matrix tested: Whole blood lysates
Summary: This paper reports the results of a phase 2a clinical study that was conducted to test the pharmacological effects of an inhibitor of p38 MAPK signaling. Phosphorylated HSP27 levels were measured as a marker of p38 pathway activation.
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| Sommers, C.D., Thompson, J.M., Guzova, J.A., Bonar, S.L., Rader, R.K., Mathialagan, S., Venkatraman, N., Holway, V.W., Kahn, L.E., Hu, G., Garner, D.S., Huang, H.C., Chiang, P.C., Schindler, J.F., Hu, Y., Meyer, D.M., Kishore, N.N. (2009) Novel Tight-Binding Inhibitory Factor-kB Kinase (IKK-2) Inhibitors Demonstrate Target-Specific Anti-Inflammatory Activities in Cellular Assays and following Oral and Local Delivery in an in Vivo Model of Airway Inflammation. J Pharmacol Exp Ther. Vol. 330(2):377-88.
Chronic obstructive pulmonary disease (COPD), asthma
Analytes tested using MSD assays: Phospho IkB
Matrix tested: Cell lysates
Summary: In this study, anti-inflammatory efficacy of inhaled Inhibitory factor-kappaB kinase 2 (IKK-2) inhibitors has been examined in a rat model of neutrophilia.
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| Wood, E.R., Shewchuk, L., Hassel, A., Nichols, J., Truesdale, A.T., Smith, D., Carter, H.L., Weaver, K., Barrett, G., Leesnitzer, T., Alvarez, E., Bardera, A.I., Alamillo, A., Cantizani, J., Martin, J., Smith, G.K., Jensen, D.E., Xie, H., Mook, R., Kumar, R., Kuntz, K. (2009) Discovery of an inhibitor of insulin-like growth factor 1 receptor activation: implications for cellular potency and selectivity over insulin receptor. Biochem Pharmacol. Vol. 78(12):1438-47.
insulin like growth factor receptor 1, insulin receptor
Analytes tested using MSD assays: Phospho Akt (Ser 473), phospho IGF-1R
Matrix tested: Primary human pre-adipocytes cell culture supernatants
Summary: In this study, a high throughput screen for an inhibitor of IGF-1R was done and a potent purine derivative was identified that was selective for IGF-1R as compared to IR and inhibited IGF-1R autophosphorylation.
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| Wu, X., Ge, H., Lemon, B., Weiszmann, J., Gupte, J., Hawkins, N., Li, X., Tang, J., Lindberg, R., Li, Y. (2009) Selective activation of FGFR4 by an FGF19 variant does not improve glucose metabolism in ob/ob mice. Proc Natl Acad Sci U S A. Vol. 106(34):14379-14384.
Fibroblast growth factor, diabetes
Analytes tested using MSD assays: Phospho and total ERK1/2
Matrix tested: Cell lysate
Summary: In this study, signaling of FGF19 (a hormone that regulates bile acid) and its receptor has been investigated in detail.
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| Xu, J., Stanislaus, S., Chinookoswong, N., Lau, Y.Y., Hager, T., Patel, J., Ge, H., Weiszmann, J., Lu, S.C., Graham, M., Busby, J., Hecht, R., Li, Y.S., Li, Y., Lindberg, R.A., Véniant, M.M. (2009) Acute glucose-lowering and insulin-sensitizing action of FGF21 in insulin resistant mouse models-Association with liver and adipose tissue effects. Am J Physiol Endocrinol Metab. 2009 Aug 25. [Epub ahead of print].
fibroblast growth factor, insulin, hepatic glucose production
Analytes tested using MSD assays: Phospho (Ser 473) and total AKT, phospho (Thr202/Tyr204) and total ERK1/2
Matrix tested: Human hepatoma (HepG2) cell culture lysates, rat hepatoma (FAO) cell lysates, mouse tissue lysates
Summary: In this study, the biological actions of recombinant fibroblast growth factor (FGF)21 and the physiological and cellular mechanisms of FGF21 functioning have been explored.
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| Yeh, C.H., Tseng, R., Zhang, Z., Cortes, J., O'Brien, S., Giles, F., Hannah, A., Estrov, Z., Keating, M., Kantarjian, H., Albitar, M. (2009) Circulating heat shock protein 70 and progression in patients with chronic myeloid leukemia. Leuk Res. Vol. 33(2):212-7.
Imatinib
Analytes tested using MSD assays: Total HSP70
Matrix tested: Human plasma
Summary: The levels of heat shock protein 70 (Hsp70) circulating in plasma of 139 chronic myeloid leukemia (CML) patients were measured in this study and correlated with clinical behavior and disease progression.
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| Yu, E.N., Traylor, Z.P., Davis, I.C. (2009) Effect of ventilation pressure on alveolar fluid clearance and beta-agonist responses in mice. Am J Physiol Lung Cell Mol Physiol. Vol. 297(4):L785-93.
tidal volume, sodium channel, adenosine
Analytes tested using MSD assays: Mouse pro-inflammatory cytokines and chemokines
Matrix tested: Mouse bronchoalveolar lavage fluid (BALF) and lung homogenates
Summary: In this study, alveolar fluid clearance was studied in mice and the effects of varying ventilation pressure as well as the response to beta-agonists were addressed.
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| Zarrinkar, P.P., Gunawardane, R.N., Cramer, M.D., Gardner, M.F., Brigham, D., Belli, B., Karaman, M.W., Pratz, K.W., Pallares, G., Chao, Q., Sprankle, K.G., Patel, H.K., Levis, M., Armstrong, R.C., James, J., Bhagwat, S.S. (2009) AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood. Vol. 114(14):2984-2992.
Sunitinib, sorafenib
Analytes tested using MSD assays: User developed assay for Phospho and Total FLT3
Matrix tested: Lysates from MV4-11 and RS4;11 cells, Tumor xenograft lysates, PBMC lysates
Summary: This paper is based on the comparison of a second generation FLT3 inhibitor (therapy for acute myeloid leukemia) with the first generation candidates in terms of potency, selectivity and pharmacokinetics.
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| Angell, R.M., Angell, T.D., Bamborough, P., Bamford, M.J., Chung, C.W., Cockerill, S.G., Flack, S.S., Jones K.L., Laine, D.I., Longstaff, T., Ludbrook, S., Pearson, R., Smith. K.J., Smee, P.A., Somers, D.O., Walker, A.L. (2008) Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes. Bioorg Med Chem Lett. Vol. 18(15):4433-4437.
p38 Kinase inhibitors, MAP kinase
Analytes tested using MSD assays: Phospho (Thr180/Tyr182) p38alpha, phospho Hsp27 (Ser15)
Matrix tested: Human lung fibroblast (HLF) cell lysates
Summary: In this study, potent biphenyl amides were prepared, their binding mode was determined by crystallography and their activity was rationalized in terms of protein conformational flexibility.
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| Brake, R., Starnes, C., Lu, J., Chen, D., Yang, S., Radinsky, R., Borges, L. (2008) Effects of palifermin on antitumor activity of chemotherapeutic and biological agents in human head and neck and colorectal carcinoma xenograft models. Mol Cancer Res. Vol. 6(8):1337-46.
FaDu, HT29, keratinocyte growth factor
Analytes tested using MSD assays: Phospho (Ser473) Akt, phospho (Thr202) ERK1/2, phospho (Tyr204) ERK1/2, phospho (Thr185) ERK1/2, phospho (Tyr187) ERK1/2
Matrix tested: Human carcinoma cell lysates
Summary: This study tested whether combining palifermin (drug for oral mucositis) with different chemotherapeutic or biological agents affected the antitumor activity of these agents in human xenograft models.
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Cao, L., Yu, Y., Darko, I., Currier, D., Mayeenuddin, L.H., Wan, X., Khanna, C., Helman, L.J. (2008) Addiction to Elevated Insulin-like Growth Factor I Receptor and Initial Modulation of the AKT Pathway Define the Responsiveness of Rhabdomyosarcoma to the Targeting Antibody. Cancer Research. Vol. 68:8039-8048.
Analytes tested using MSD assays: Phospho and total Akt, phospho and total EGFR, IGF-1R
Matrix tested: Human rhabdomyosarcoma tumor lysates and cell supernatants, human skeletal muscle tissue lysates, mouse xenograft tumor lysates
Summary: In this study, the determinants of cellular response to a humanized anti-IGF-IR antibody were investigated.
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| Cho, H.K., Black, S.C., Looper, D., Shi, M., Kelly-Sullivan, D., Timofeevski, S., Siegel, K., Yu, X.H., McDonnell, S.R., Chen, P., Yie, J., Ogilvie, K.M., Fraser, J., Briscoe, C.P. (2008) Pharmacological characterization of a small-molecule inhibitor of c-Jun kinase. Am J Physiol Endocrinol Metab. Vol. 295(5):1142-51.
Type 2 Diabetes, insulin resistance, diet induced obese mice
Analytes tested using MSD assays: Phospho (Ser63) c-Jun, Insulin, phospho (Ser307) IRS-1, cytokines
Matrix tested: Mouse plasma
Summary: In this paper, a novel small molecule inhibitor for JNK, called Compound A, has been characterized and its ability to improve insulin resistance and reduce weight gain in high-fat fed mice has been demonstrated.
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| Dahut, W. L., Scripture, C., Posadas, E., Jain, L., Gulley, J. L., Arlen, P.M., Wright, J.J., Yu, Y., Cao L., Steinberg, S.M., Aragon-Ching, J.B., Venitz, J., Jones, E., Chen, C.C., Figg, W. D. (2008) A Phase II Clinical Trial of Sorafenib in Androgen-Independent Prostate Cancer. Clin Cancer Res. Vol. 14:209-214.
Prostrate specific antigen, PSA
Analytes tested using MSD assays: Phospho ERK
Matrix tested: Bone marrow biopsy lysates, HT-29 cell lysates
Summary: This paper states the results of a phase II clinical trial conducted to assess the anticancer efficacy, toxicity, and pharmacokinetics of sorafenib drug in metastatic AIPC.
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| Eccles, S.A., Massey, A., Raynaud, F.I., Sharp, S.Y., Box, G., Valenti, M., Patterson, L., de Haven Brandon, A., Gowan, S., Boxall, F., Aherne, W., Rowlands, M., Hayes, A., Martins, V., Urban, F., Boxall, K., Prodromou, C., Pearl, L., James, K., Matthews, T.P., Cheung, K.M., Kalusa, A., Jones, K., McDonald, E., Barril, X., Brough, P.A., Cansfield, J.E., Dymock, B., Drysdale, M.J., Finch, H., Howes, R., Hubbard, R.E., Surgenor, A., Webb, P., Wood, M., Wright, L., Workman, P. (2008) NVP-AUY922: a novel heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis. Cancer Res. Vol. 68(8):2850-60.
extracellular signal-regulated kinase 1/2, hypoxia inducible factor 1alpha, HIF-1a, HIF1a, HIF1a, HIF-1a, Heat shock protein, HSP90
Analytes tested using MSD assays: Phospho Akt, total Akt, HSP72, ERBB2, ERK1/2, HIF-1alpha
Matrix tested: Tumor xenograft lysates
Summary: In this paper, the in vitro activity and in vivo pharmacokinetic, pharmacodynamic, and efficacy profiles of NVP-AUY922 (HSP90 inhibitor) was investigated in several human tumor cell lines and xenografts with different molecular pathologies.
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| Folkes, A.J., Ahmadi, K., Alderton, W.K., Alix, S., Baker, S.J., Box, G., Chuckowree, I.S., Clarke, P.A., Depledge, P., Eccles, S.A., Friedman, L.S., Hayes, A., Hancox, T.C., Kugendradas, A., Lensun, L., Moore, P., Olivero, A.G., Pang, J., Patel, S., Pergl-Wilson, G.H., Raynaud, F.I., Robson, A., Saghir, N., Salphati, L., Sohal, S., Ultsch, M.H., Valenti, M., Wallweber, H.J., Wan, N.C., Wiesmann, C., Workman, P., Zhyvoloup, A., Zvelebil, M.J., Shuttleworth, S.J. (2008) The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer. J Med Chem. Vol. 51(18):5522-32.
PI3-Kinase, PI3K, phosphatidylinositol-3-kinase, mTOR
Analytes tested using MSD assays: Phospho (Ser 473) and total Akt
Matrix tested: Human tumor cell line lysates
Summary: In this study, several thieno[3,2-d]pyrimidine derivatives were synthesized and tested as inhibitors of PI3 kinase in human cancer cell lines.
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| Grund, E.M., Kagan, D., Tran, C.A., Zeitvogel, A., Starzinski-Powitz, A., Nataraja, S., Palmer, S.S. (2008) Tumor necrosis factor-alpha regulates inflammatory and mesenchymal responses via mitogen-activated protein kinase kinase, p38, and nuclear factor kappaB in human endometriotic epithelial cells. Mol Pharmacol. Vol. 73(5):1394-404.
qPCR, Quantitative PCR, Western Blot, Nuclear Factor kappa B, Mitogen Activated Protein Kinase, TNF, tumor necrosis factor, MAPK
Analytes tested using MSD assays: Phospho (Thr180/Tyr182) and total p38, phospho (Ser468) NFkB, phospho (Ser473) and total Akt, phospho (Thr202/Tyr204) and total ERK, GMCSF, IL-6, MCP-1, IL-8
Matrix tested: Cell lysates, cell culture supernatants
Summary: In this study, the response of 12Z immortalized human epithelial endometriotic cells to TNF-alpha was investigated with the rationale that TNF-alpha signaling regulates secretion of inflammation and invasion mediators.
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| Hendriks, B.S, Hua, F., Chabot, J.R. (2008) Analysis of mechanistic pathway models in drug discovery: p38 pathway. Biotechnol Prog. Vol. 24(1):96-109.
Tumor necrosis factor, TNFa, TNF-a, TNF-a, TNFa, TNFalpha
Analytes tested using MSD assays: Phospho p38, phospho (Ser15, Ser78 and Ser82) Hsp27, TNF-alpha
Matrix tested: U937 cell lysates
Summary: In this study, the authors created a novel signaling model of lipopolysaccharide (LPS) induced p38 signaling to answer specific drug discovery questions regarding target prioritization, inhibitor simulation, model robustness and co-drugging.
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| Huang, J.W., Zhang, Z., Wu, B., Cellitti, J.F., Zhang, X., Dahl, R., Shiau, C.W., Welsh, K., Emdadi, A., Stebbins, J.L., Reed, J.C., Pellecchia, M. (2008) Fragment-Based Design of Small Molecule X-Linked Inhibitor of Apoptosis Protein Inhibitors. J Med Chem. Vol. 51(22):7111-8.
X-linked inhibitor of apoptosis protein, XIAP, peptide mimetics
Analytes tested using MSD assays: Cleaved and total caspase 3
Matrix tested: Human breast cancer cell (MDA-MB 231 cell line) lysates
Summary: In this study, a new method for the discovery of small molecule inhibitors has been described in which virtual libraries are generated by replacing individual amino acids in an iterative manner with more drug-like scaffolds, the top scoring compounds are chemically synthesized and experimentally tested with NMR spectroscopy.
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| Jia, Y., Quinn, C.M., Kwak, S.,Talanian, R.V. (2008) Current In Vitro Kinase Assay Technologies: The Quest for a Universal Format. Curr Drug Discov Technol. Vol. 5(1): 59-69.
radiometric, Scintillation Proximity Assay (SPA), gel permeation, Homogeneous Time Resolved Fluorescence (HTRF), DELFIA, AlphaScreen, LANCE, fluorescence quench, HitHunter, Kinase-Glo
Summary: This paper provides a review on the principles, strengths and weaknesses of the major commercial assay systems available for kinase activity, and the potential applications of these systems in drug discovery.
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| Kattla, J.J., Carew, R.M., Heljic, M., Godson, C., Brazil, D.P. (2008) Protein kinase B/Akt activity is involved in renal TGF-{beta}1-driven epithelial-mesenchymal transition in vitro and in vivo. Am J Physiol Renal Physiol. Vol. 295(1): 215-25.
diabetic nephropathy, transforming growth factor beta 1, TGF-b1, TGF-1b, TGF-1beta, GSK-3b, GSK3b,GSK-3ß, GSK3ß, glycogen synthase kinase
Analytes tested using MSD assays: Phospho (Ser 473) AKT, phospho (Ser9) GSK-3beta
Matrix tested: Cell lysates
Summary: In this study, the mechanisms underlying the pathophysiology of diabetic neuropathy has been investigated with regard to protein kinase B activation and its role in mediating the pro-fibrotic action of TGF-beta1 in kidney.
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| Lam, L.T., Wright, G., Davis, R.E., Lenz, G., Farinha, P., Dang, L., Chan, J.W., Rosenwald, A., Gascoyne, R.D., Staudt, L.M. (2008) Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-{kappa}B pathways in subtypes of diffuse large B-cell lymphoma. Blood. Vol. 111(7):3701-13.
Nuclear factor kappaB
Analytes tested using MSD assays: Phospho (Tyr705) STAT3
Matrix tested: Cell lysates
Summary: In this study, a pathogenic role of IL-6 and IL-10 signaling through the JAK/STAT3 pathway was investigated in a subgroup of diffuse large B-cell lymphoma.
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Lorenzi, P.L., Llamas, J., Gunsior, M., Ozbun, L., Reinhold, W.C., Varma, S., Ji, H., Kim, H., Hutchinson, A.A., Kohn, E.C., Goldsmith, P.K., Birrer, M.J., Weinstein, J.N. (2008) Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines. Mol Cancer Ther. Vol. (10):3123-8.
Analytes tested using MSD assays: User developed assay for asparagine synthetase (ASNS) on MSD avidin plates
Matrix tested: Cell lysates
Summary: In this study, the authors determined the conditions under which asparagine synthetase (ASNS) predicts L-asparaginase (L-ASP) activity in a large sample set of ovarian cancer cell lines with the rationale that ASNS serves as a biomarker of L-ASP activity. L-ASP is a FDA approved drug for cancer.
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McGrath, M.F., Bogosian, G., Fabellar, A.C., Staub, R.L., Vicini, J.L., Widger, L.A. (2008) Measurement of bovine somatotropin (bST) and insulin-like growth factor-1 (IGF-1) in bovine milk using an electrochemiluminescent assay. J Agric Food Chem. Vol. 56(16):7044-8.
Analytes tested using MSD assays: Bovine somatotropin (bST), Insulin-like growth factor-1 (IGF-1)
Matrix tested: Milk
Summary: This study is based on the development of highly sensitive immunoassays on the MSD platform to measure peptide hormones such as bST and IGF-1 in bovine milk.
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| Oliveira, V., Romanow, W.J., Geisen, C., Otterness, D.M., Mercurio, F., Wang, H.G., Dalton, W.S., Abraham, R.T. (2008) A Protective Role for the Human SMG-1 Kinase against Tumor Necrosis Factor-alpha induced Apoptosis. J Biol Chem. Vol. 283(19):13174-13184.
phosphoinositide 3 kinase related kinase, Nonsense mediated mRNA decay
Analytes tested using MSD assays: Cleaved caspase-3
Matrix tested: U2OS osteosarcoma cell lysates
Summary: In this study, the mechanism of action of hSMG-1 in providing protection from TNF-alpha induced apoptosis has been investigated.
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| Peifer, C., Alessi, D.R. (2008) Small-Molecule Inhibitors of PDK1. ChemMedChem. Vol. 3(12):1810-38.
3-phosphoinositide dependent protein kinase 1
Analytes tested using MSD assays: Phospho (Thr308) AKT
Matrix tested: COS7 cell lysates
Summary: This article reviews a comprehensive collection of small molecules that have been reported to inhibit PDK1, and provides detail on their biological characterization in terms of activity and selectivity for PDK1.
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| Rottenberg, S., Jaspers, J.E., Kersbergen, A., van der Burg, E., Nygren, A.O., Zander, S.A., Derksen, P.W., de Bruin, M., Zevenhoven, J., Lau, A., Boulter, R., Cranston, A., O'Connor, M.J., Martin, N.M., Borst, P., Jonkers, J. (2008) High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. PNAS Vol. 105(44):17079-17084.
Poly ADP ribose polymerase 1
Analytes tested using MSD assays: PARP1
Matrix tested: Tumor xenograft lysates
Summary: In this study, the effects of PARP inhibitor, AZD2281, have been tested in a genetically engineered mouse model (GEMM) for BRCA1-associated breast cancer.
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| Sasiela, C.A., Stewart, D.H., Kitagaki, J., Safiran, Y.J., Yang, Y., Weissman, A.M., Oberoi, P., Davydov, I.V., Goncharova, E., Beutler, J.A., McMahon, J.B., O'Keefe, B.R. (2008) Identification of inhibitors for MDM2 ubiquitin ligase activity from natural product extracts by a novel high-throughput electrochemiluminescent screen. J Biomol Screen. Vol. 13(3):229-37.
High throughput screening, MDM2, ubiquitin
Analytes tested using MSD assays: Polyubiquitinated E3, Phospho and total p53, cleaved PARP, cleaved caspase 3
Matrix tested: Cell lysates
Summary: The focus of this study was to conduct a high throughput screen of natural product extracts for inhibitors of MDM2 ubiquitin ligase activity using ECL technology from MSD.
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| Schneider, C., Docke, W.D., Zollner, T.M., Rose, L. (2008) Chronic Mouse Model of TMA-Induced Contact Hypersensitivity. J Invest Dermatol. Vol. 129(4):899-907.
Trimellitic anhydride (TMA), eczema
Analytes tested using MSD assays: IFN-gamma, IL-1beta, IL-4, IL-12p35, IL-13, TNF-alpha
Matrix tested: Mouse ear homogenates
Summary: The focus of this paper was to establish a T-cell-dependent skin inflammation mouse model for atopic dermatitis reflecting the pathology of chronic human disease.
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| Ward, T.H., Cummings, J., Dean, E., Greystoke, A., Hou, J.M., Backen, A., Ranson, M., Dive, C. (2008) Biomarkers of apoptosis. British J Cancer. Vol. 99:841-846.
cytokeratins, nucleosomal DNA, circulating tumour cells
Summary: This is a review article that provides a discussion on the pros and cons of different methods to detect different components of apoptosis as potential biomarkers of cell death. Serological assays, potential biomarkers and novel multiplex technologies have been discussed in this regard.
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| Weissman, A.M., Yang, Y., Kitagaki, J., Sasiela, C.A., Beutler, J.A., O'Keefe, B.R. (2008) Inhibiting Hdm2 and Ubiquitin-Activating Enzyme: Targeting the Ubiquitin Conjugating System in Cancer. In The Ubiquitin System in Health and Disease. Springer Berlin Heidelberg.
Ubiquitin, Hdm2, Mdm2, PYR-41, Pyrazone 41, ubiquitin activating enzyme, 5-deazaflavins
Summary: This paper provides a summary of the ongoing efforts of the authors in identifying inhibitors of Hdm2 E3 and E1 enzyme activity by high throughput screening using enzymatic as well as cell-based assays.
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| Bolten, C. W., Blanner, P.M., McDonald, W.G., Staten, N.R., Mazzarella, R.A., Arhancet, G.B., Meier, M.F., Weiss, D.J., Sullivan, P.M., Hromockyj, A.E., Kletzien, R.F., Colca, J.R. (2007) Insulin Sensitizing Pharmacology of Thiazolidinediones Correlates with Mitochondrial Gene Expression rather than Activation of PPARg. Gene Regulation and Systems Biology. Vol. 1:73-82.
thiazolidinedione, insulin sensitization, diabetes
Analytes tested using MSD assays: Phospho Akt (Ser473) / Total Akt
Matrix tested: Human hepatoma (HUH7) cell lysates
Summary: This study compares the general effects of two thiazolidinedione (TZD) analogs that vary in their ability to activate PPARg in an effort to determine the mechanisms necessary for the pharmacology of these compounds and the transcriptional regulation that are correlated with insulin sensitization.
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| Chan, F., Sun, C., Perumal, M., Nguyen, Q.D., Bavetsias, V., McDonald, E., Martins, V., Wilsher, N.E., Raynaud, F.I., Valenti, M., Eccles, S., Te Poele, R., Workman, P., Aboagye, E.O., Linardopoulos, S. (2007) Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. Mol Cancer Ther. Vol. 6(12 Pt 1):3147-57.
Type 2 Diabetes, insulin resistance, Akt, FOXO1A
Analytes tested using MSD assays: Phospho (Ser10) Histone 3 and total Histone 3
Matrix tested: Tumor xenograft lysates
Summary: In this paper, the authors examined the properties of CCT129202, which is representative of a new series of imidazopyridine small-molecule inhibitors of Aurora kinase in multiple human tumor cell lines.
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| Gowan, S.M., Hardcastle, A., Hallsworth, A.E., Valenti, M.R., Hunter, L.J., de Haven Brandon, A.K., Garrett, M.D., Raynaud, F., Workman, P., Aherne, W., Eccles, S.A. (2007) Application of Meso Scale Technology for the Measurement of Phosphoproteins in Human Tumor Xenografts. Assay and Drug Dev Technol. Vol. 5 (3):391-401.
GSK3beta, GSK-3b, GSK3b, GSK-3ß, GSK3ß
Analytes tested using MSD assays: Phospho (Ser 473) and total AKT, phospho (Ser 9) and total GSK-3beta
Matrix tested: Tumor xenograft lysates
Summary: The focus of this study was to develop and optimize the MESO SCALE DISCOVERY® platform to quantify changes in phospho Akt and phospho GSK-3beta in response to a PI3-kinase inhibitor, LY294002, both in vitro and in vivo.
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| Koivunen, P., Tiainen, P., Hyvarinen, J., Williams, K.E., Sormunen, R., Klaus, S.J., Kivirikko, K.I., Myllyharju, J. (2007) An endoplasmic reticulum transmembrane prolyl 4-hydroxylase is induced by hypoxia and acts on hypoxia-inducible factor alpha. J Biol Chem. Vol. 282(42):30544-52.
Hypoxia inducible factor, HIF-1a, HIF1a, HIF1alpha, HIF-1a, HIF1a
Analytes tested using MSD assays: HIF-1alpha
Matrix tested: Cell lysates
Summary: This study is based on the characterization of a novel human Prolyl 4-hydroxylase (P4H), which possesses a transmembrane domain. P4Hs acts on hypoxia-inducible factor alpha subunits leading to its degradation.
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| Lu, Y., Young, J., Meng, Y.G.(2007) Electrochemiluminescence to detect surface proteins on live cells. Current Op Pharmacology. Vol. 7:541-546.
Flow cytometry, ELISA
Analytes tested using MSD assays: CD20 expression, B-cell markers, CXCR4, IL-2Ralpha, ICAM-1
Matrix tested: CHO cells, HEK293 cells, CD4+ T-cells, adherent HUVEC cells
Summary: In this study, MSD electrochemiluminescence platform has been used as an alternative to flow cytometry and cell-based ELISAs to detect surface proteins on live cells. The main advantages of ECL application that have been mentioned here include higher throughput than flow cytometry, ability to grow as well as assay cells in a single plate, ability to incorporate wash step with suspension cells, elimination of centrifugation steps, ease of use, elimination of detaching step in tissue culture of adherent cells and better signal to noise ratio.
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| Martin, S.E., Jones, T.L., Thomas, C.L., Lorenzi, P.L., Nguyen, D.A., Runfola, T., Gunsior, M., Weinstein, J.N., Goldsmith, P.K., Lader, E., Huppi, K., Caplen, N.J. (2007) Multiplexing siRNAs to compress RNAi-based screen size in human cells. Nucleic Acids Res. Vol. 35(8):57.
B-RAF, serine threonine kinase, glycogen synthase kinase 3 beta, GSK-3b, GSK3beta, GSK3b, Microtubule associated protein kinase kinase 2, MAPKK2, Epidermal growth factor receptor, tumor protein p53, small interfering RNA
Analytes tested using MSD assays: BRAF, GSK-3beta, MEK2, BAD, EGFR, HIF-1alpha, MET, TP53 (tumor protein p53)
Matrix tested: MDA-MB-231 cell lysates, HCT-116 lysates
Summary: This paper is based on the development of a multiplex-based approach for screening of siRNAs, which in turn may be helpful in the rapid identification of candidate gene targets.
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Poitout, L., Brault, V., Sackur, C., Bernetiere, S., Camara, J., Plas, P., Roubert, P. (2007) Identification of a novel series of benzimidazoles as potent and selective antagonists of the human melanocortin-4 receptor. Bioorg Med Chem Lett. Vol. 17(16): 4464-70.
Analytes tested using MSD assays: Cyclic AMP (cAMP)
Matrix tested: Cell lysates
Summary: In this study, authors tested a novel series of melanocortin-4 receptor antagonists to be used for treatment of cachexia related syndromes.
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| Raynaud, F.I., Eccles, S., Clarke, P.A., Hayes, A., Nutley, B., Alix, S., Henley, A., Di-Stefano, F., Ahmad, Z., Guillard, S., Bjerke, L.M., Kelland, L., Valenti, M., Patterson, L., Gowan, S., de Haven Brandon, A., Hayakawa, M., Kaizawa, H., Koizumi, T., Ohishi, T., Patel, S., Saghir, N., Parker, P., Waterfield, M., Workman, P. (2007) Pharmacological Characterization of a Potent Inhibitor of Class I Phosphotidylinositide 3-Kinases. Cancer Res. Vol. 67(12): 5840-5850.
PI3K, PI3 kinase, phosphatidylinositide 3 kinase
Analytes tested using MSD assays: Phospho (Ser473) and total Akt
Matrix tested: Tumor xenograft lysates
Summary: The detailed pharmacologic properties of a novel synthetic small molecule of the pyridofuropyrimidine class, PI103, have been examined in this paper. PI103 is a potent and selective inhibitor of class I PI3-Kinase and shows antitumor activity in several human tumor xenograft models.
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| Schuck, S., Gerl M.J., Ang, A., Manninen, A., Keller, P., Mellman, I., Simons, K. (2007) Rab10 is Involved in Basolateral Transport in Polarized Madin-Darby Canine Kidney Cells. Traffic. Vol. 8(1):47-60.
basolateral membrane, biosynthetic transport, Golgi, Rab GTPases, Madin Darby canine kidney cells
Analytes tested using MSD assays: User developed assay for VSV-G (vesicular stomatitis virus glycoprotein)
Matrix tested: MDCK cell lysates
Summary: In this study, role of small GTPase, Rab10, in conducting biosynthetic transport was investigated in polarized epithelial cells.
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| Torhan, A.S., Cheewatrakoolpong, B., Kwee, L., Greenfeder, S. (2007) Cloning and characterization of the hamster and guinea pig nicotinic acid receptors. J Lipid Res. Vol. 48(9):2065-71.
cAMP, niacin
Analytes tested using MSD assays: Cyclic AMP
Matrix tested: CHO-K1 cell supernatants
Summary: In this study, orthologs of GPR109A, a receptor for nicotinic acid, were identified and characterized from hamster and guinea pig DNA, and their mRNA expression, ligand binding as well as functionality were examined.
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| Yang, R., Wilcox, D.M., Haasch, D.L., Jung, P.M., Nguyen, P.T., Voorbach, M.J., Doktor, S., Brodjian, S., Bush, E.N., Lin, E., Jacobson, P.B., Collins, C.A., Landschulz, K.T., Trevillyan, J.M., Rondinone, C.M., Surowy, T.K. (2007) Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor gamma coactivator 1 beta and increases plasma triglyceride despite reduced glucose and insulin levels in diet-induced obese mice. J Biol Chem. Vol. 282(31):22765-74.
Glycolysis, gluconeogenesis, obesity, liver, insulin resistance, Akt, Western blot
Analytes tested using MSD assays: Phospho c-Jun
Matrix tested: Mouse liver homogenates
Summary: In this study, RNA interference was done to investigate the specific role of hepatic JNK1 in contributing to insulin resistance in diet induced obese (DIO) mice.
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| Athauda, G., Giubellino, A., Coleman, J.A., Horak, C., Steeg, P.S., Lee, M.J., Trepel, J., Wimberly, J., Sun, J., Coxon, A., Burgess, T.L., Bottaro, D.P. (2006) c-Met Ectodomain Shedding Rate Correlates with Malignant Potential. Clin Cancer Res. Vol. 12(14):4154-4162.
Hepatocyte growth factor receptor, cMet, cancer
Analytes tested using MSD assays: Customer developed assay on MSD Streptavidin plates for ectodomain of c-Met
Matrix tested: Cell culture supernatants
Summary: This study tested the hypothesis that c-Met overexpression in cancer might result in increased ectodomain shedding, which in turn could be a biomarker of tumor progression.
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| Khakoo, A.Y., Pati, S., Anderson, S.A., Reid, W., Elshal, M.F., Rovira, I.I., Nguyen, A.T., Malide, D., Combs, C.A., Hall, G., Zhang, J., Raffeld, M., Rogers, T.B., Stetler-Stevenson, W., Frank, J.A., Reitz. M., Finkel, T. (2006) Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma. J Exp Med. Vol. 203(5):1235-47.
glycogen synthase kinase 3 beta, GSK-3b, GSK3beta, GSK3b
Analytes tested using MSD assays: ERK1/2, GSK-3beta
Matrix tested: Tumor xenograft lysates
Summary: This paper focused on investigating a novel anti-tumorigenic effect of mesenchymal stem cells (MSC) and the role of Akt in mediating this effect.
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| Lu, Y., Wong, W.L., Meng, Y.G. (2006) A high throughput electrochemiluminescent cell-binding assay for therapeutic anti-CD20 antibody selection. J Immunological Methods. Vol. 314(1-2):74-9.
antibody humanization, anti-CD20, WIL2 cells
Analytes tested using MSD assays: CD20
Matrix tested: CD-20 expressing CHO cells
Summary: In this study, the development and characterization of a high throughput ECL based cell-binding assay for measuring antibody binding to live suspension and adherent cells has been described.
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| Phelps, T., Anthes, J.C., Correll, C.C. (2006) Characterization of adenosine receptors in the human bladder carcinoma T24 cell line. Euro J Pharmacol. Vol. 536(1-2):28-37.
A2A, A2B, A1, A3
Analytes tested using MSD assays: Cyclic AMP (cAMP)
Matrix tested: Cell culture supernatants
Summary: In this study, the authors investigated the expression of the adenosine receptor subtypes present in the T24 human urinary bladder urothelial carcinoma cell line, which is a model system for elucidating molecular mechanisms associated with pathologic bladder conditions.
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| Prevost, G.P., Lonchampt, M.O., Holbeck, S., Attoub, S., Zaharevitz, D., Alley, M., Wright, J., Brezak, M.C., Coulomb, H., Savola, A., Huchet, M., Chaumeron, S., Nguyen, Q.D., Forgez, P., Bruyneel, E., Bracke, M., Ferrandis, E., Roubert, P., Demarquay, D., Gespach, C., Kasprzyk, P.G. (2006) Anticancer Activity of BIM-46174, a New Inhibitor of the Heterotrimeric Ga/Gßg Protein Complex. Cancer Res. Vol. 66(18):9227-9234.
Guanine binding protein coupled receptors, GPCR, anti-cancer, chemotherapy
Analytes tested using MSD assays: Cleaved caspase-3, cleaved poly(ADP-ribose) polymerase (PARP)
Matrix tested: Cell lysates
Summary: In this paper, the authors characterized a selective inhibitor of heterotrimeric G-protein complex called BIM-46174, which causes caspase-3-dependent apoptosis and poly(ADP-ribose) polymerase cleavage in cancer cell lines.
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| Qin, P., Tang, X., Elloso, M.M., Harnish, D.C. (2006) Bile acids induce adhesion molecule expression in endothelial cells through activation of reactive oxygen species, NF-kB, and p38. Am J Physiol Heart Circ Physiol. Vol. 291:741-747.
Inter Cellular Adhesion Molecule 1, vascular cell adhesion molecule 1, Inter-Cellular Adhesion Molecule 1, E-selectin, Nuclear factor kappa B, NF-kappaB
Analytes tested using MSD assays: ICAM-1, VCAM-1
Matrix tested: Human umbilical vein endothelial cell (HUVEC) culture supernatant
Summary: This paper examined whether elevated levels of bile acids in the liver induces hepatic and vascular inflammation, and the mechanism of action for the same.
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| Ross S., Chen, T., Yu, V., Tudor, Y., Zhang, D., Liu, L., Tamayo, N., Dominguez, C., Powers, D. (2006) High-content screening analysis of the p38 pathway: profiling of structurally related p38alpha kinase inhibitors using cell-based assays. Assay Drug Dev Technol. Vol. 4(4):397-409.
p38alpha, P38-alpha, MK2, HSP27, SW1353 chondrocytes, baby hamster kidney (BHK) cells
Analytes tested using MSD assays: TNF-alpha
Matrix tested: Cell culture supernatants
Summary: This paper is based on the use of cellular imaging assays to measure inhibition of different components of the p38 pathway, with pyrimidinone, imidazopyrimidine, and triazolopyrimidine inhibitors.
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Davydov, I.V., Kenten, J.H., Safiran, Y.J., Nelson, S. Swenerton, R., Oberoi, P., Biebuyck, H.A. (2005) In vitro screening for substrates of the N-end rule-dependent ubiquitylation. Methods in Enzymology. Vol. 399:415-432.
Analytes tested using MSD assays: User developed assay to screen ubiquitylation substrates
Matrix tested: Rabbit reticulocyte lysate based transcription-translation system
Summary: In this study, a systematic high-throughput method was developed to screen for substrates of ubiquitylation and using this system, a library of 18000 cDNA clones was screened.
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Kenten J.H., Davydov I.V., Safiran Y.J., Stewart D.H., Oberoi P., Biebuyck, H.A. (2005) Assays for high-throughput screening of E2 and E3 ubiquitin ligases. Methods in Enzymology. Vol. 399:682-701.
Analytes tested using MSD assays: E2 ligase activity, E3 ligase activity
Matrix tested: Assay buffer
Summary: In this paper, the authors developed electrochemiluminescence based ubiquitylation assays on the MSD platform to measure the activities of E2 ubiquitin conjugating enzymes and E3 class ubiquitin ligases.
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Vieira, O.V., Verkade, P., Manninen, A., Simons, K. (2005) FAPP2 is involved in the transport of apical cargo in polarized MDCK cells. J Cell Biol. Vol. 170(4): 521-526.
Analytes tested using MSD assays: YFP-labeled glycosylated (GL) glycosylphosphatidylinositol (GPI)
Matrix tested: Cell lysates
Summary: This study investigated the mechanisms of polarized trafficking, and the functional role of phosphatidylinositol-4-phosphate and its adaptor proteins in the delivery of biosynthetic cargo from the Golgi complex to the cell surface in Madin-Darby canine kidney (MDCK) cells.
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| Davydov, I.V., Woods, D., Safiran, Y.J., Oberoi, P., Fearnhead, H.O., Fang, S., Jensen, J.P., Weissman, A.M., Kenten, J.H., Vousden, K.H. (2004) Assay for ubiquitin ligase activity: high-throughput screen for inhibitors of HDM2. J Biomol Screen. Vol. 9(8):695-703.
HDM2, Mdm2, ubiquitin, E3, p53
Analytes tested using MSD assays: HDM2 (Mdm2) assay
Matrix tested: Assay buffer
Summary: In this study, a high throughput assay for E3 ligase activity (HDM2) was developed using electrochemiluminescence technology to identify inhibitors of E3 ligase.
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| Russello, S.V. (2004) Assessing cellular protein phosphorylation: high throughput drug discovery technologies. Assay Drug Dev Technol. Vol. 2(2):225-35.
ELISA, dissociation enhanced lanthanide fluorescence immunoassay (DELFIA), MSD, Searchlight, Luminex, ACLARA eTag, Cytoblot, in-cell western (ICW), high content screening (HCS), Bio-Plex
Summary: This is a review article wherein the different high throughput methods that are available to screen for phosphoproteins using cell lysates or whole cells have been described in detail.
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| Williams, C. (2004) cAMP Detection Methods in HTS: Selecting the best from the rest. Nature Reviews: Drug Discovery Vol. 3(2):125-35.
GPCR, Flashplate technology, HTRF, FRET, amplified luminescence assay
Summary: This is a review article on the most common systems that are available for the detection of and highlights the practical and theoretical aspects that are important in the application of these methods for high-throughput screening.
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| Wainer, I.W., Beigi, F., Moaddel, R. (2003) High throughput screening using G-protein coupled receptors as the target. Drug Discovery World. Summer 2003.
GPCR
Summary: This is a review article on the different methods and technologies that are available for high-throughput screening of G-protein coupled receptors.
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* Pub Med (www.pubmed.gov) is a service of the U.S. National Library of Medicine and the National Institutes of Health
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