2. Academic Validation
  3. Discovery of indirubin derivatives as new class of DRAK2 inhibitors from high throughput screening

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

  • Bioorg Med Chem Lett. 2016 Jun 1;26(11):2719-23. doi: 10.1016/j.bmcl.2016.03.111.
Myoung Eun Jung 1,  Byung Jin Byun 1,  Hye-Mi Kim 2,  Joo Yun Lee 1,  Jin-Hee Park 3,  Nari Lee 2,  You Hwa Son 1,  Sang Un Choi 1,  Kyung-Min Yang 4,  Seong-Jin Kim 4,  Kwangho Lee 2,  Yong-Chul Kim 5,  Gildon Choi 6
Affiliations

Affiliations

  • 1 Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea.
  • 2 Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology (UST), 217 Gajeong-Ro, Yuseong-gu, Daejeon 305-350, Republic of Korea.
  • 3 School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
  • 4 Department of Biomedical Science, CHA University of Medicine and Science, Kyunggi-do 463-400, Republic of Korea.
  • 5 School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: yongchul@gist.ac.kr.
  • 6 Drug Discovery Division, Korea Research Institute of Chemical Technology, 141 Gajeong-Ro, Yuseong-gu, Daejeon 305-600, Republic of Korea; Medicinal Chemistry and Pharmacology, Korea University of Science and Technology (UST), 217 Gajeong-Ro, Yuseong-gu, Daejeon 305-350, Republic of Korea. Electronic address: gchoi@krict.re.kr.
PMID: 27106709 DOI: 10.1016/j.bmcl.2016.03.111
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=0.003μM). We also propose that compound 16 may bind to the ATP-binding site of the Enzyme based on Enzyme kinetics and molecular docking studies.

Keywords

DRAK1; DRAK2; Indirubin; Inhibitor; Kinase.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-122629
    99.93%, DAPK Inhibitor