BROWSE

Related Scientist

Researcher

김진희
분자활성 촉매반응 연구단
more info

Identification of lead small molecule inhibitors of glycogen synthase kinase-3 beta using a fragment-linking strategy

Cited 4 time in webofscience Cited 0 time in scopus
293 Viewed 22 Downloaded
Title
Identification of lead small molecule inhibitors of glycogen synthase kinase-3 beta using a fragment-linking strategy
Author(s)
Jinhee Kim; Yonghoon Moon; Sungwoo Hong
Publication Date
2016-12
Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v.26, no.23, pp.5669 - 5673
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Abstract
Glycogen synthase kinase-3 beta (GSK3β) kinase serves as a promising therapeutic target for the treatment of various human diseases, such as diabetes, obesity, and Alzheimer's disease. In this study, we report lead GSK3β inhibitors identified using a fragment-linking strategy. Through the systematic exploration, a six-atom chain unit bearing the rigid double bond was found to be a suitable linker connecting two fragments, which enables favorable contacts with backbone groups of residues in the pockets. As a consequence, potent GSK3β inhibitor 9i was found with IC50 values of 19 nM. The binding mode analysis indicates that the activities of the inhibitors appear to be achieved by the establishment of multiple hydrogen bonds and hydrophobic interactions in the ATP-binding site of GSK3β. The good biochemical potencies and structural uniqueness of the inhibitors support consideration in the further study to optimize the biological activity. © 2016 Elsevier Ltd.
URI
https://pr.ibs.re.kr/handle/8788114/3227
ISSN
0960-894X
Appears in Collections:
Center for Catalytic Hydrocarbon Functionalizations(분자활성 촉매반응 연구단) > Journal Papers (저널논문)
Files in This Item:
[BMCL] Glycogen synthase kinase-3 beta.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse