3区 · 医学
Article
作者: Castro-Perez, Jose ; Tang, Wei ; Rosenbach, Mark ; Sok, Andrea ; Ma, Xiuying ; Bopp, Charlene ; Zhou, Gaochao ; London, Clare ; Ren, Ning ; Metzger, Joe ; Wisniewski, Tom ; Maxwell, Carrie Ann ; Yin, Lina ; Struthers, Mary ; Verras, Andreas ; van Koppen, Chris J. ; Hu, Qingzhong ; Stribling, Sloan ; Salituro, Gino ; Chen, Qing ; Lassman, Mike ; Hoyt, Scott B. ; Gibson, Jack ; Hajdu, Richard ; Cai, Tian-Quan ; Clemas, Joe ; McMasters, Daniel ; McLaughlin, Theresa ; Xiong, Yusheng ; Szeto, Daphne ; Hartmann, Rolf W. ; Tata, Jim ; Forrest, Gail ; Tung, Elaine ; Liang, Gui-Bai ; Petrilli, Whitney ; Pai, Lee-Yuh ; Buist, Nicole
Hit-to-lead efforts resulted in the discovery of compound 19, a potent CYP11B2 inhibitor that displays high selectivity vs related CYPs, good pharmacokinetic properties in rat and rhesus, and lead-like physical properties. In a rhesus pharmacodynamic model, compound 19 displays robust, dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels.