A randomized, placebo-controlled study of the pharmacokinetics, pharmacodynamics, and tolerability of the oral JAK2 inhibitor fedratinib (SAR302503) in healthy volunteers.

Zhang M, Xu CR, Shamiyeh E, Liu F, Yin J, von Moltke LL, Smith WB.
Journal   J Clin Pharmacol.
Species  
Analytes Measured   STAT3
Matrix Tested   Cell lysates
Year   2013
Volume  
Page Numbers  
Application   Immunogenicity , Phosphoproteins
Abstract
Fedratinib (SAR302503/TG101348) is a Janus kinase 2 (JAK2)-selective inhibitor in clinical development for the treatment of myelofibrosis. In this randomized, placebo-controlled, Phase 1 study, the pharmacokinetics, pharmacodynamics and tolerability of ascending single doses of fedratinib (10-680 mg) were assessed in healthy male subjects. Fedratinib was rapidly absorbed, with peak plasma concentration observed approximately 3 hours after dosing. The mean terminal half-life of fedratinib was approximately 67 hours, which was unaffected by dose. Fedratinib exposure increased in a greater than dose-proportional manner. Suppression of signal transducer and activator of transcription 3 (STAT3) phosphorylation, indicative of JAK2 inhibition, was observed at 3 hours post-dose for subjects in the 300, 500, and 680 mg groups, with the level of suppression increasing with dose. The relationship between fedratinib exposure and suppression of STAT3 phosphorylation was described using an inhibitory effect sigmoid Emax model, with an EC50 of 1,210 ng/mL in healthy subjects. The most common adverse events were mild gastrointestinal toxicities.

View Publications

Related Products

Phospho-STAT Panel Kit
STAT3, STAT4, STAT5a/b | Human, Mouse, Rat
Singleplex
Phospho-STAT3 (Tyr705) Kit
STAT3 | Human
Singleplex
Total STAT3 Kit
STAT3 | Human
Singleplex
ERK-STAT3 Cascade Whole Cell Lysate Kit
ERK-1/2, MEK 1/2, STAT3 | Human, Mouse, Rat
Multiplex
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters