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 (10.6 h), 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)

Product information

CAS Number: 1257628-77-5

Molecular Weight: 532.56

Formula: C29H27F3N6O

Synonym:

GZD-824

GZD 824

Chemical Name: 4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}-3-(2-{1H-pyrazolo[3,4-b]pyridin-5-yl}ethynyl)benzamide

Smiles: CN1CCN(CC2=CC=C(C=C2C(F)(F)F)NC(=O)C2=CC(C#CC3=CN=C4NN=CC4=C3)=C(C)C=C2)CC1

InChiKey: TZKBVRDEOITLRB-UHFFFAOYSA-N

InChi: InChI=1S/C29H27F3N6O/c1-19-3-5-22(14-21(19)6-4-20-13-24-17-34-36-27(24)33-16-20)28(39)35-25-8-7-23(26(15-25)29(30,31)32)18-38-11-9-37(2)10-12-38/h3,5,7-8,13-17H,9-12,18H2,1-2H3,(H,35,39)(H,33,34,36)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

Products are for research use only. Not for human use.