| Identification | Back Directory | [Name]
GZD 824 | [CAS]
1257628-77-5 | [Synonyms]
GZD824
GZD-824
GZD8824
GZD 824
GZD-824 Free
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 | [Molecular Formula]
C29H27F3N6O | [MDL Number]
MFCD26142930 | [MOL File]
1257628-77-5.mol | [Molecular Weight]
532.559 |
| Chemical Properties | Back Directory | [Boiling point ]
630.4±55.0 °C(Predicted) | [density ]
1.39±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : ≥ 100 mg/mL (187.77 mM) | [form ]
A crystalline solid | [pka]
9.04±0.40(Predicted) | [color ]
Off-white to yellow |
| Hazard Information | Back Directory | [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).1 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.1 | [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. | [Application]
Olverembatinib is able to inhibit wild-type BCR-ABL1 kinase and a wide range of related mutants, including the T315I mutant, which makes it a potential treatment for TKI-resistant CML patients. In addition, Olverembatinib is also being studied for the treatment of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and solid tumors. | [Definition]
GZD 824 (Olverembatinib), another third-generation BCR-ABL tyrosine kinase inhibitor (TKI), was approved in 2021 in China for patients with T315I positive chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP). Like ponatinib, olverembatinib inhibits multikinases, including B-RAF, DDR1, FGFR, Flt3, KIT, PDGFRα/β, RET, and SRC.
| [General Description]
Class: non-receptor tyrosine kinase
Treatment: CML
Elimination half-life = 17.5–36.5 h
| [Synthesis]
In a recent patent, the synthesis of olverembatinib began with a Sonogashira coupling reaction of commercially available alkyne 24.1 with pyridinium bromide 24.2 to afford ester 24.3 in 98% yield. The N-Boc group of carbonate 24.3 was cleaved by refluxing in a mixture of MeOH and water to afford pyrazole 24.4 in 91% yield. Finally, potassium tert-butoxide-mediated amide formation with aniline 24.5 afforded olverembatinib (24) in 88% yield.
 | [target]
BCR-ABL | [References]
[1] XIAOMEI REN. 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]. Journal of Medicinal Chemistry, 2013, 56 3: 879-894. DOI: 10.1021/jm301581y |
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