Friday, December 4, 2015

Drugs in Clinical Pipeline: GSK2256098 | FAK Inhibitor | Cancer Drug

GSK2256098 [2-[5-Chloro-2-(2-isopropyl-5-methyl-2H-pyrazol-3-yiamino)-pyridin-4-ylamino]-N-methoxy-benzamide] as a potent, selective, reversible, and ATP competitive inhibitor of FAK (Focal adhesion kinase) activity (apparent Ki = 0.4 nM). The cocrystal structure reveals compound bound in the ATP binding pocket of FAK [1].

GSK2256098: 2D and 3D Structure

The potent enzymatic activity translates to cellular activity when  IC50 values for reducing cellular phospho-FAK levels (pFAK-(Tyr 397)) were determined by ELISA. GSK2256098 inhibited cellular pFAK with IC50 values from 2-15 nM and level of pFAK remained low over time in the continues presence of the compound [1].

1H NMR (Estimated) for GSK2256098

1. Auger, K. R. et. al. The Focal Adhesion Kinase Inhibitor GSK2256098: a Potent and Selective Inhibitor for the Treatment of Cancer. Eur J Cancer 2012, 48, 118.