Olverembatinib (GZD824)

Catalog No: 24046

CAS Number: 1257628-77-5

Purity: 98% Min.

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).

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Chemical Information

Name	Olverembatinib (GZD824)
Iupac Chemical Name	3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide
Synonyms	GZD824; GZD 824; GZD-824; Olverembatinib;
Molecular Formula	C29H27F3N6O
Molecular Weight	532.56
Smile	CC1=CC=C(C=C1C#CC2=CN=C3C(C=NN3)=C2)C(NC4=CC=C(C(C(F)(F)F)=C4)CN5CCN(CC5)C)=O
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)
CAS Number	1257628-77-5
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Formulation	Off-white solid
Purity	98% Min.
Storage	Dry, dark and at 0 - 4℃ for short term (days to weeks) or -20℃ for long term (months to years).
Solubility	Soluble in DMSO
Handling	Refer to MSDS
Shipping Condition	Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
HS Code	2934200090

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Targets
Mechanism
Cell study
Animal study
Clinical study

1: Tang H, Jia W, Jia S, Dong R, Gao S, Feng J, Dong H, Gu H, Zhang T, Yuan R, Liu X, Cheng L, Zhou S, Gao G. A new chemotherapy-free regimen of olverembatinib in combination with venetoclax and dexamethasone for newly diagnosed Ph+ acute lymphoblastic leukemia: Preliminary outcomes of a prospective study. Am J Hematol. 2024 Mar 14. doi: 10.1002/ajh.27289. Epub ahead of print. PMID: 38482543.

2: Zhu H, Hixson P, Ma W, Sun J. Pharmacology of LRRK2 with type I and II kinase inhibitors revealed by cryo-EM. Cell Discov. 2024 Jan 23;10(1):10. doi: 10.1038/s41421-023-00639-8. Erratum in: Cell Discov. 2024 Feb 26;10(1):23. PMID: 38263358; PMCID: PMC10805800.

3: Sanz Murillo M, Villagran Suarez A, Dederer V, Chatterjee D, Alegrio Louro J, Knapp S, Mathea S, Leschziner AE. Inhibition of Parkinson's disease-related LRRK2 by type I and type II kinase inhibitors: Activity and structures. Sci Adv. 2023 Dec;9(48):eadk6191. doi: 10.1126/sciadv.adk6191. Epub 2023 Dec 1. PMID: 38039358; PMCID: PMC10691770.

4: Ding J, Li W. Case report: Olverembatinib monotherapy: the chemotherapy-free regimen for an elderly patient with relapsed Ph-positive acute lymphoblastic leukemia. Front Pharmacol. 2023 Nov 16;14:1320641. doi: 10.3389/fphar.2023.1320641. PMID: 38035030; PMCID: PMC10687180.

5: Fan S, Wang L, Lu Y, Li Z. Olverembatinib combined with blinatumomab in treating T315I-mutated Philadelphia chromosome-positive acute lymphoblastic leukemia: two-case report. Ann Hematol. 2024 Feb;103(2):525-532. doi: 10.1007/s00277-023-05519-5. Epub 2023 Nov 9. PMID: 37940719.

6: Hijiya N, Mauro MJ. Asciminib in the Treatment of Philadelphia Chromosome- Positive Chronic Myeloid Leukemia: Focus on Patient Selection and Outcomes. Cancer Manag Res. 2023 Aug 23;15:873-891. doi: 10.2147/CMAR.S353374. PMID: 37641687; PMCID: PMC10460573.

7: Yan Y, Qu S, Liu J, Li C, Yan X, Xu Z, Qin T, Jia Y, Pan L, Gao Q, Jiao M, Li B, Gale RP, Xiao Z. Olverembatinib for myeloid/lymphoid neoplasm associated with eosinophilia and FGFR1 rearrangement. Leuk Lymphoma. 2023 Sep;64(9):1605-1610. doi: 10.1080/10428194.2023.2226277. Epub 2023 Jun 24. PMID: 37354441.

8: Li X, Zhang J, Liu F, Liu T, Zhang R, Chen Y, Guo Y, Fang Y, Xu X, Pui CH, Zhu X. Olverembatinib Treatment in Pediatric Patients With Relapsed Philadelphia-Chromosome-Positive Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):660-666. doi: 10.1016/j.clml.2023.04.012. Epub 2023 May 11. PMID: 37301632.

9: Senapati J, Sasaki K, Issa GC, Lipton JH, Radich JP, Jabbour E, Kantarjian HM. Management of chronic myeloid leukemia in 2023 - common ground and common sense. Blood Cancer J. 2023 Apr 24;13(1):58. doi: 10.1038/s41408-023-00823-9. PMID: 37088793; PMCID: PMC10123066.

10: Liu C, Zhang X, Mao L, Qian J, Xiao F, Ye X, Wei J, Ye X, Jin J, Yu W. Olverembatinib in relapsed Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia: a study of 5 cases. Leuk Lymphoma. 2023 Jun;64(6):1208-1211. doi: 10.1080/10428194.2023.2197534. Epub 2023 Apr 17. PMID: 37067187.

11: Xiang D, Zhao T, Wang J, Cao Y, Yu Q, Liu L, Yu H, Li X, Li N, Yi Y, Gong X. Determination of olverembatinib in human plasma and cerebrospinal fluid by an LC-MS/MS method: Validation and clinical application. J Pharm Biomed Anal. 2023 Jun 15;230:115382. doi: 10.1016/j.jpba.2023.115382. Epub 2023 Mar 31. PMID: 37060798.

12: Scalzulli E, Carmosino I, Costa A, Bisegna ML, Martelli M, Breccia M. Management of Chronic Myeloid Leukemia Patients in Later Lines: The Role of Ponatinib and New Compounds. Clin Lymphoma Myeloma Leuk. 2023 Jun;23(6):420-425. doi: 10.1016/j.clml.2023.03.004. Epub 2023 Mar 20. PMID: 37029061.

13: Yang Z, Liu C, Hu Y, Liu H, Li J, Wu L, Liu Q, Zheng Y, Huang P, Wang Y. Tyrosine kinase inhibitors combined with venetoclax and azacytidine as an effective therapy for de novo lymphoid blast phase-chronic myeloid leukemia. Leuk Res. 2023 Apr;127:107039. doi: 10.1016/j.leukres.2023.107039. Epub 2023 Feb 12. PMID: 36812660.

14: Jiang Q, Li Z, Qin Y, Li W, Xu N, Liu B, Zhang Y, Meng L, Zhu H, Du X, Chen S, Liang Y, Hu Y, Liu X, Song Y, Men L, Chen Z, Niu Q, Wang H, Lu M, Yang D, Zhai Y, Huang X. Correction: Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial. J Hematol Oncol. 2023 Feb 20;16(1):13. doi: 10.1186/s13045-023-01414-8. Erratum for: J Hematol Oncol. 2022 Aug 18;15(1):113. PMID: 36803531; PMCID: PMC9942283.

15: Zhang T, Zhou H, Xu M, Qian C, Sun A, Wu D, Xue S. Combination venetoclax and olverembatinib (HQP1351) as a successful therapeutic strategy for relapsed/refractory (R/R) mixed-phenotype blast phase of chronic myeloid leukemia. Ann Hematol. 2023 Apr;102(4):973-975. doi: 10.1007/s00277-023-05110-y. Epub 2023 Feb 6. PMID: 36745193.

16: Tan X, Wen Q, Chen G, Wan K, Liu X, Ma YY, Wang MH, Zhang X, Zhang C. Novel third-generation tyrosine kinase inhibitor for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a case study. Anticancer Drugs. 2023 Apr 1;34(4):599-604. doi: 10.1097/CAD.0000000000001455. Epub 2022 Nov 21. PMID: 36730312; PMCID: PMC9997626.

17: Yin Z, Liao M, Yan R, Li G, Ou R, Liu Z, Zhong Q, Shen H, Zhu Y, Xie S, Zhang Q, Liu S, Huang J. Transcriptome- and metabolome-based candidate mechanism of BCR-ABL-independent resistance to olverembatinib in Philadelphia chromosome- positive acute lymphoblastic leukemia. Funct Integr Genomics. 2023 Jan 31;23(1):53. doi: 10.1007/s10142-023-00980-x. PMID: 36717477.

18: Yu Z, Lei Z, Yao X, Wang H, Zhang M, Hou Z, Li Y, Zhao Y, Li H, Liu D, Zhai Y. Potential drug-drug interaction of olverembatinib (HQP1351) using physiologically based pharmacokinetic models. Front Pharmacol. 2022 Dec 13;13:1065130. doi: 10.3389/fphar.2022.1065130. PMID: 36582520; PMCID: PMC9792776.

19: Qian H, Gang D, He X, Jiang S. A review of the therapeutic role of the new third-generation TKI olverembatinib in chronic myeloid leukemia. Front Oncol. 2022 Dec 8;12:1036437. doi: 10.3389/fonc.2022.1036437. PMID: 36568202; PMCID: PMC9772831.

20: Öziskender R, Eşkazan AE. Olverembatinib in chronic myeloid leukemia. Drugs Today (Barc). 2022 Nov;58(11):531-538. doi: 10.1358/dot.2022.58.11.3441854. PMID: 36422514.

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24046 - Olverembatinib (GZD824) | CAS 1257628-77-5

Olverembatinib (GZD824)

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