Analysis of mechanistic pathway models in drug discovery: p38 pathway.

Hendriks, B.S, Hua, F., Chabot, J.R.
Journal   Biotechnol Prog.
Species  
Analytes Measured   HSP27 , p38
Matrix Tested   U937 cell lysates
Year   2008
Volume   24
Page Numbers   96-109
Application   Phosphoproteins
Abstract
Mechanistic models of signal transduction have emerged as valuable tools for untangling complex signaling networks and gaining detailed insight into pathway dynamics. The natural extension of these tools is for the design of therapeutic strategies. We have generated a novel computational model of lipopolysaccharide-induced p38 signaling in the context of TNF-alpha production in inflammatory disease. Using experimental measurement of protein levels and phospho-protein time courses, populations of model parameters were estimated. With a collection of parameter sets, reflecting virtual diversity, we step through analysis of the p38 signaling pathway model to answer specific drug discovery questions regarding target prioritization, inhibitor simulation, model robustness and co-drugging. We demonstrate that target selection cannot be assessed independently from inhibitor mechanism of action and is also linked with robustness to cellular variability. Finally, we assert that in the face of parameter uncertainty one can still uncover consistent findings that can guide drug discovery efforts.

View Publications

Related Products

MAP Kinase Whole Cell Lysate Kit
ERK-1/2, JNK, p38 | Human, Mouse, Rat
Multiplex
Phospho/Total p38 Whole Cell Lysate Kit
p38 | Human, Mouse, Rat
Multiplex
MAP Kinase (Total Protein) Whole Cell Lysate Kit
ERK-1/2, JNK, p38 | Human
Multiplex
Phospho-p38 Whole Cell Lysate Kit
p38 | Human, Mouse, Rat
Singleplex
Phospho (Ser82)/Total HSP27 Whole Cell Lysate Kit
HSP27 | Human
Multiplex
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters