Discovery of indirubin derivatives as new class of DRAK2 inhibitors from high throughput screening. Issue 11 (1st June 2016)

• Record Type: Journal Article
• Authors: Jung, Myoung Eun; Byun, Byung Jin; Kim, Hye-Mi; Lee, Joo Yun; Park, Jin-Hee; Lee, Nari; Son, You Hwa; Choi, Sang Un; Yang, Kyung-Min; Kim, Seong-Jin; Lee, Kwangho; Kim, Yong-Chul; Choi, Gildon
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 11(2016)
• Page Start: 2719
• Page End: 2723
• Publication Date: 2016-06-01
• Subjects: Indirubin -- DRAK1 -- DRAK2 -- Kinase -- Inhibitor; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.03.111
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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, compound16 exhibited the most potent inhibitory activity against DRAK2 (IC50 = 0.003 μM). We also propose that compound16 may bind to the ATP-binding site of the enzyme based on enzyme kinetics and molecular docking studies.