Discovery of indirubin derivatives as new class of DRAK2 inhibitors from high throughput screening

Abstract

DRAK2 is a serine/threonine kinase belonging to the death- associated protein kinase (DAPK) family and has emerged as a promising drug target for the treatment of autoimmune diseases and cancers. To identify small molecule inhibitors for DRAK2, we performed a high throughput screening campaign using in-house chemical library and identified indirubin-3'-monoximes as novel class of DRAK2 inhibitors. Among the compounds tested, compound 16 exhibited the most potent inhibitory activity against DRAK2 (IC50 = 0.003 mu M). We also propose that compound 16 may bind to the ATP-binding site of the enzyme based on enzyme kinetics and molecular docking studies. (C) 2016 Elsevier Ltd. All rights reserved.