Journal of Medicinal Chemistry p. 2114 - 2130 (2020)
Update date:2022-08-15
Topics:
Yang, Jianzhang
Shibu, Marthandam Asokan
Kong, Lulu
Luo, Jinfeng
Badrealamkhan, Farheen
Huang, Yanhui
Tu, Zheng-Chao
Yun, Cai-Hong
Huang, Chih-Yang
Ding, Ke
Lu, Xiaoyun
ZAK is a new promising target for discovery of drugs with activity against antihypertrophic cardiomyopathy (HCM). A series of 1,2,3-triazole benzenesulfonamides were designed and synthesized as selective ZAK inhibitors. One of these compounds, 6p binds tightly to ZAK protein (Kd = 8.0 nM) and potently suppresses the kinase function of ZAK with single-digit nM (IC50 = 4.0 nM) and exhibits excellent selectivity in a KINOMEscan screening platform against a panel of 403 wild-type kinases. This compound dose dependently blocks p38/GATA-4 and JNK/c-Jun signaling and demonstrates promising in vivo anti-HCM efficacy upon oral administration in a spontaneous hypertensive rat (SHR) model. Compound 6p may serve as a lead compound for new anti-HCM drug discovery.
View MoreShanghai Hongbang Medical Technology CO.,. Ltd
Contact:13671516988 /18917636693
Address:Room1, No67 Building, Yongde Road369, Wujing Town, Minhang Districy, Shanghai CIty, China.
Feiyang Biotechnology Co., Ltd.
Contact:+86-533-7866339
Address:Qilu Chemistry Park, 200m north of Management Community Building of Park
Chengdu NoVi Biotechnology Co., Ltd.
Contact:13551243286/028-81458053
Address:NO.168-1-224 JULONG ROAD WUHOU DISTRICT, CHENGDU CITY,SICHUAN PROVINCE
Shandong Shouguang Songchuan Industrial Additives Co.,Ltd
Contact:+86-536-8566856
Address:Shouguang,Shandong,China
Shandong Shouguang Songchuan Industrial Additives Co.,Ltd
Contact:+86-536-8566856
Address:Shouguang,Shandong,China
Doi:10.1021/acs.jafc.5b05733
(2016)Doi:10.1246/bcsj.52.955
(1979)Doi:10.1016/S0022-328X(00)90632-6
(1980)Doi:10.1021/jo01117a019
(1956)Doi:10.1016/j.bioorg.2018.05.026
(2018)Doi:10.1021/jo01130a014
(1953)