1257628-77-5

Basic information

• Product Name: GZD 824
• Synonyms: 4-Methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide;3-(2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide;GZD8824;GZD-824 Free;GZD 824;GZD824;GZD-824
• CAS NO: 1257628-77-5
• Molecular Formula: C₂₉H₂₇F₃N₆O
• Molecular Weight: 532.5594896
• Product Categories: Inhibitors
• Mol File: 1257628-77-5.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 630.4±55.0 °C(Predicted)
• Appearance: /
• Density: 1.39±0.1 g/cm3(Predicted)
• PKA: 9.04±0.40(Predicted)
• CAS DataBase Reference: GZD 824(CAS DataBase Reference)
• NIST Chemistry Reference: GZD 824(1257628-77-5)
• EPA Substance Registry System: GZD 824(1257628-77-5)

Safety Data

• Hazardous Substances Data: 1257628-77-5(Hazardous Substances Data)

Usage

Description

GZD-824 is an orally available inhibitor of a broad spectrum of Bcr/Abl tyrosine kinase mutants including T315I (IC50s = 0.34 and 0.68 nM for wild-type Bcr/Abl and Bcr/AblT315I, respectively). It has been shown to suppress the proliferation of Bcr/Abl-positive K562 and Ku812 human chronic myelogenous leukemia cells (IC50s = 0.2 and 0.13 nM, respectively) and induce tumor regression in mouse xenograft tumor models driven by either wild-type or mutant Bcr/Abl.

Uses

GZD824 is a orally bioavailable inhibitor that targets phosphorylated and non-phosphorylated Breakpoint Cluster Region-Abelson (Bcr-Abl) kinases. It is a COVID19-related research product.

Upstream product

• 694499-26-8 4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethylaniline 
• 1207351-08-3 5-((trimethylsilyl) ethynyl)-1H-pyrazolo[3,4-b]pyridine 
• 875781-17-2 5-bromo-7-azaindazole 
• 90347-66-3 methyl 3-iodo-4-methylbenzoate 
• 943320-50-1 3-iodo-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl) phenyl)benzamide 
• 1207351-15-2 5-ethynyl-1H-pyrazolo[3,4-b]pyridine 

Downstream Products

• 1421783-64-3 3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide bismethanesulfonic acid 

Relevant articles and documents

PROCESS FOR PREPARING ALKYNYL-CONTAINING COMPOUND AND INTERMEDIATE THEREOF

Disclosed are processes for preparing alkylnyl-containing compounds of Formula (I) as shown below, intermediates and related compounds thereof. Pharmaceutical compositions comprising the compounds and methods of treating cancer thereof are also disclosed.

HETEROCYCLIC ALKYNYL BENZENE COMPOUNDS AND MEDICAL COMPOSITIONS AND USES THEREOF

The heterocyclic alkynyl benzene compounds of formula (I), their pharmaceutically acceptable salts and stereoisomers thereof, as well as application in preparing drugs for preventing or treating tumors. The compounds can overcome the clinically induced resistance against Gleevec.

Identification of GZD824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-Abelson (Bcr-Abl) kinase and overcomes clinically acquired mutation-induced resistance against imatinib

Bcr-AblT315I mutation-induced imatinib resistance remains a major challenge for clinical management of chronic myelogenous leukemia (CML). Herein, we report GZD824 (10a) as a novel orally bioavailable inhibitor against a broad spectrum of Bcr-Abl mutants including T315I. It tightly bound to Bcr-AblWT and Bcr-AblT315I with Kd values of 0.32 and 0.71 nM, respectively, and strongly inhibited the kinase functions with nanomolar IC50 values. The compound 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. It 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-AblWT or the mutants and significantly improved the survival of mice bearing an allograft leukemia model with Ba/F3 cells harboring Bcr-AblT315I. GZD824 represents a promising lead candidate for development of Bcr-Abl inhibitors to overcome acquired imatinib resistance.