Name: GZD824
Brand: BOC Sciences
Rating: 5 (1 reviews)

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Price

Stock

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$--

In stock

Purity

>98%

IUPACName

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

Synonyms

GZD824; GZD 824; GZD-824.

InChI Key

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)

Canonical SMILES

CC1=C(C=C(C=C1)C(=O)NC2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)C#CC4=CC5=C(NN=C5)N=C4

1.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.

Ren X1, Pan X, Zhang Z, Wang D, Lu X, Li Y, Wen D, Long H, Luo J, Feng Y, Zhuang X, Zhang F, Liu J, Leng F, Lang X, Bai Y, She M, Tu Z, Pan J, Ding K. J Med Chem. 2013 Feb 14;56(3):879-94. doi: 10.1021/jm301581y. Epub 2013 Jan 28.

Bcr-Abl(T315I) 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-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. 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-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).

Good evening, I want to ask one technical question. would you please tell me the mechanism of action of GZD824 ?

Similar to other Bcr-Abl inhibitors, GZD824 binds to the ATP-binding pocket of the kinase, preventing it from transferring phosphate groups and disrupting downstream signaling pathways that drive CML growth. Additionally, it has the unique ability to target both the phosphorylated and non-phosphorylated forms of Bcr-Abl, potentially contributing to its effectiveness against resistant forms of CML.

30/9/2016

Hi, I want to know its Potency, can you tell me something about it?

Highly effective against both wild-type and T315I mutant Bcr-Abl (IC50 of 0.2 nM and 0.13 nM in K562 and Ku812 cells, respectively)

17/2/2018

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂