0 53

Cited 0 times in

Identification of highly selective type II kinase inhibitors with chiral peptidomimetic tails

Authors
 Seo-Jung Han  ;  Jae Eun Jung  ;  Do Hee Oh  ;  Minsup Kim  ;  Jae-Min Kim  ;  Kyung-Sook Chung  ;  Hee-Soo Han  ;  Jeong-Hun Lee  ;  Kyung-Tae Lee  ;  Hee Jin Jeong  ;  In Ho Park  ;  Eunkyeong Jeon  ;  Jeon-Soo Shin  ;  Dongkeun Hwang  ;  Art E Cho  ;  Duck-Hyung Lee  ;  Taebo Sim 
Citation
 JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, Vol.37(1) : 1257-1277, 2022-04 
Journal Title
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
ISSN
 1475-6366 
Issue Date
2022-04
MeSH
Animals ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Mice ; Peptidomimetics* / pharmacology ; Protein Kinase Inhibitors / pharmacology ; Tail ; src-Family Kinases
Keywords
DSS-induced colitis ; Lck ; Type-II kinase
Abstract
Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor 7a potently inhibited Lck kinase with great selectivity (IC50 of 23.0 nM). It was found that 7a and its derivatives possessed high selectivity for Lck over even structurally conserved all Src family kinases. We also observed that 7a inhibited Lck activation in Jurkat T cells. Moreover, 7a was found to alleviate clinical symptoms in DSS-induced colitis mice. This study provides a novel insight into the design of selective type II kinase inhibitors by adopting chiral peptidomimetic moieties on the tail region.
Full Text
https://www.tandfonline.com/doi/full/10.1080/14756366.2022.2068148
DOI
10.1080/14756366.2022.2068148
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Park, Inho(박인호)
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
Sim, Taebo(심태보)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188575
사서에게 알리기
  feedback

qrcode

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

Browse

Links