1421783-64-3

Basic information

• Product Name: GZD824
• Synonyms: Benzamide, 4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]-, methanesulfonate (1:2);4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]-, methanesulfonate (1:2) -Benzamide GZD824 Dimesylate;GZD824 GZD824DIMESYLATE;GZD824 GZD824DIMESYLATE Benzamide, 4-methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]-, meth;4-Methyl-N-[4-[(4-methyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl]benzamide methanesulfonate (1:2)
• CAS NO: 1421783-64-3
• Molecular Formula: C31H35F3N6O7S2
• Molecular Weight: 724.7708096
• Product Categories: Inhibitors
• Mol File: 1421783-64-3.mol
• Article Data: 3

Chemical Properties

• Appearance: /
• Solubility: ≥36.25 mg/mL in DMSO; ≥33.95 mg/mL in H2O with ultrasonic; ≥4.71 mg/mL in EtOH with ultrasonic
• CAS DataBase Reference: GZD824(CAS DataBase Reference)
• NIST Chemistry Reference: GZD824(1421783-64-3)
• EPA Substance Registry System: GZD824(1421783-64-3)

Safety Data

• Hazardous Substances Data: 1421783-64-3(Hazardous Substances Data)

Usage

Description

GZD824 is an orally bioavailable Bcr-Abl inhibitor, specifically targeting both Bcr-Abl(WT) and Bcr-Abl(T315I). It is a compound that has gained significant attention in the context of COVID-19-related research, showcasing its potential in addressing various health concerns.

Uses

Used in Pharmaceutical Industry:
GZD824 is used as a Bcr-Abl inhibitor for the treatment of certain cancers, particularly those involving the Bcr-Abl protein. Its ability to inhibit both wild-type and T315I-mutated Bcr-Abl makes it a valuable asset in the fight against cancer.
Used in COVID-19 Research:
GZD824 is used as a research compound in the context of COVID-19. Its potential applications in this field are currently being explored, with the aim of understanding its effectiveness in combating the virus and contributing to the development of new therapeutic strategies.

Biological Activity

gzd824 is an orally bioavailable inhibitor of bcr-abl with ic50 values of 0.34 and 0.68 nm for bcr-ablwt and bcr-ablt315i, respectively [1].bcr-abl is a fused protein that interacts with the interleukin-3 receptorβ(c) subunit and has tyrosine kinase activity. abl activates cell cycle-related proteins and enzymes and increases cell division. bcr-abl inhibits dna repair and causes genomic instability.gzd824 is an orally bioavailable bcr-abl inhibitor. gzd824 exhibited high affinity with kd values of 0.32 and 0.71 nm for bcr-ablwt and bcr-ablt315i, respectively. gzd824 inhibited bcr-abl with ic50 values of 0.34, 0.68, 0.27, 0.71, 0.15, 0.35, 0.29 and 0.35 nm for bcr-ablwt, bcr-ablt315i, bcr-able255k, bcr-ablg250e, bcr-ablq252h, bcr-ablh396p, bcr-ablm351t and bcr-ably253f, respectively. in a competitive binding assay, gzd824 bound to the atp-binding sites of native abl with kd values of 0.32 and 0.34 nm for non-phosphorylated and phosphorylated abl. in stably transformed ba/f3 cells, gzd824 potently inhibited cells growth with ic50 values of 1.0 and 7.1 nm for bcr-ablwt and bcr-ablt315i expressed cells, respectively [1].in mouse xenograft tumor models, gzd824 inhibited tumor growth. in mice bearing an allograft leukemia model, gzd824 significantly increased survival [1].

references

ren x, pan x, zhang z, et al. 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. j med chem, 2013, 56(3): 879-894.

Upstream product

• 1207351-08-3 5-((trimethylsilyl) ethynyl)-1H-pyrazolo[3,4-b]pyridine 
• 875781-17-2 5-bromo-7-azaindazole 
• 694499-26-8 4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethylaniline 
• 90347-66-3 methyl 3-iodo-4-methylbenzoate 
• 75-75-2 methanesulfonic acid 
• 1257628-77-5 3-(2-(1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide 
• 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 

Relevant articles and documents

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.

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.