GZD824 CAS：1257628-77-5

Olverembatinib,also known as GZD824,is a novel orally bioavailable inhibitor against a broad spectrum of Bcr-Abl mutants including T315I.GZD824 tightly bound to Bcr-Abl(WT)and Bcr-Abl(T315I)with K(d)values of 0.32 and 0.71 nM, respectively,and strongly inhibited the kinase functions with nanomolar IC(50) values.GZD824 potently suppressed proliferation of Bcr-Abl-positive K562 and Ku812 human CML cells with IC(50)values of 0.2 and 0.13 nM, respectively.GZD824 also displayed good oral bioavailability (48.7%),a reasonable half-life(10.6h), and promising in vivo antitumor efficacy.It induced tumor regression in mouse xenograft tumor models driven by Bcr-Abl(WT)or the mutants and significantly improved the survival of mice bearing an allograft leukemia model with Ba/F3 cells harboring Bcr-Abl(T315I).GZD824 represents a promising lead candidate for development of Bcr-Abl inhibitors to overcome acquired imatinib resistance.(J Med Chem.2013 Feb 14;56(3):879-94).

msds---GZD824