Design, synthesis and biological evaluation of novel tetrahydrothieno [2,3-c]pyridine substitued benzoyl thiourea derivatives as PAK1 inhibitors in triple negative breast cancer

Autor:	Dahong Yao, Jian Huang, Jinhui Wang, Zhendan He, Jin Zhang
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	high-throughput virtual screening pak1 inhibitor anti-proliferation cell cycle arrests breast cancer Therapeutics. Pharmacology RM1-950
Zdroj:	Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 35, Iss 1, Pp 1524-1538 (2020)
Druh dokumentu:	article
ISSN:	1475-6366 1475-6374 14756366
DOI:	10.1080/14756366.2020.1797710
Popis:	The overexpression of P21-activated kinase 1 (PAK1) is associated with poor prognosis in several cancers, which has emerged as a promising drug targets. Based on high-throughput virtual screening strategy, tetrahydrothieno [2,3-c]pyridine scaffold was identified as an initial lead for targeting PAK1. Herein we reported our structure-based optimisation strategy to discover a potent PAK1 inhibitor (7j) which displayed potent PAK1 inhibition and antiproliferatory activity in MDA-MB-231 cells. 7j induced obviously G2/M cell cycle arrest via PAK1-cdc25c-cdc2 pathway, and also inhibited MAPK-ERK and MAPK-JNK cascade to induce MDA-MB-231 cell death. Together, these results provided a novel chemical scaffold as PAK1 inhibitor for breast cancer treatment.
Databáze:	Directory of Open Access Journals
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