Flumatinib free base | CAS#895519-90-1 | BCR-ABL inhibitor

MedKoo Cat#: 206184 | Name: Flumatinib free base

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Flumatinib, also known as HHGV678 , is a selective inhibitor of BCR-ABL/PDGFR/KIT. Flumatinib is currently in Phase I and II clinical trials in China for the treatment of chronic myelogenous leukemia (CML). Flumatinib effectively overcomes drug resistance of certain KIT mutants. Flumatinib mesylate can reduce the expression of C-MYC, HIF-1 α and VEGF in U266 cell line in a time- and dose-dependent manners.

Chemical Structure

Flumatinib free base

CAS#895519-90-1 (free base)

Theoretical Analysis

MedKoo Cat#: 206184

Name: Flumatinib free base

CAS#: 895519-90-1 (free base)

Chemical Formula: C29H29F3N8O

Exact Mass: 562.2416

Molecular Weight: 562.59

Elemental Analysis: C, 61.91; H, 5.20; F, 10.13; N, 19.92; O, 2.84

Price and Availability

Size	Price	Availability
10mg	USD 350.00	2 Weeks
25mg	USD 650.00	2 Weeks
50mg	USD 950.00	2 Weeks

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Related CAS #

895519-90-1 (free base) 895519-91-2 (mesylate)

Synonym

HHGV678; HHGV 678 ; HHGV-678; HH-GV-678; Flumatinib;

IUPAC/Chemical Name

N-(6-methyl-5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)pyridin-3-yl)-4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzamide

InChi Key

BJCJYEYYYGBROF-UHFFFAOYSA-N

InChi Code

InChI=1S/C29H29F3N8O/c1-19-26(38-28-34-9-7-25(37-28)21-4-3-8-33-16-21)15-23(17-35-19)36-27(41)20-5-6-22(24(14-20)29(30,31)32)18-40-12-10-39(2)11-13-40/h3-9,14-17H,10-13,18H2,1-2H3,(H,36,41)(H,34,37,38)

SMILES Code

CC1=C(NC2=NC=CC(C3=CN=CC=C3)=N2)C=C(NC(C4=CC(C(F)(F)F)=C(CN5CCN(C)CC5)C=C4)=O)C=N1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

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.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# CAS No. 895519-90-1 (Flumatinib) 895519-91-2 (Flumatinib Mesylate)

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Flumatinib (HHGV678) is an orally available, selective inhibitor of Bcr-Abl. Flumatinib inhibits c-Abl, PDGFRβ and c-Kit with IC50s of 1.2 nM, 307.6 nM and 665.5 nM, respectively.

In vitro activity:

In 32D-V559D + Y823D cells, the phosphorylation levels of KIT, ERK1/2, and STAT3 were strongly inhibited by flumatinib, but not imatinib or sunitinib (Fig. 2). Similar findings were observed in 32D-V559D + N822K and 32D-V559D + A829P cells (Fig. S1). These results collectively show that flumatinib is capable of overcoming the imatinib and sunitinib resistance conferred by certain secondary activation loop mutations in vitro. Reference: Cancer Sci. 2014 Jan; 105(1): 117–125. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317885/

In vivo activity:

In contrast, treatments with imatinib (150 mg/kg, b.i.d.) and flumatinib (75 mg/kg, q.d. and b.i.d.) extended the median survival to 23.5 (P = 0.23), 25.5 (P = 0.061), and 25.5 (P < 0.05) days, relative to the vehicle-treated group, respectively (Fig. 3). In addition, the survival of mice treated with flumatinib (75 mg/kg, b.i.d.) was significantly improved compared with mice treated with imatinib (150 mg/kg, q.d.; P < 0.01) or sunitinib (50 mg/kg, q.d.; P < 0.01). Reference: Cancer Sci. 2014 Jan; 105(1): 117–125. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4317885/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	177.75

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 562.59 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zhao J, Quan H, Xu Y, Kong X, Jin L, Lou L. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25. doi: 10.1111/cas.12320. Epub 2014 Jan 4. PMID: 24205792; PMCID: PMC4317885.

In vitro protocol:

In vivo protocol:

1: Zhang L, Meng L, Liu B, Zhang Y, Zhu H, Cui J, Sun A, Hu Y, Jin J, Jiang H, Zhang X, Li Y, Liu L, Zhang W, Liu X, Gu J, Qiao J, Ouyang G, Liu X, Luo J, Jiang M, Xie X, Li J, Zhao C, Zhang M, Yang T, Wang J. Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase III, Randomized, Open-label, Multi-center FESTnd Study. Clin Cancer Res. 2021 Jan 1;27(1):70-77. doi: 10.1158/1078-0432.CCR-20-1600. Epub 2020 Sep 14. PMID: 32928796. 2: Gao H, Li L, Mu J, Tan J, Chen R. Efficacy of Flumatinib in CML Patients with F359V/C Mutation. Indian J Hematol Blood Transfus. 2023 Apr;39(2):344-346. doi: 10.1007/s12288-022-01585-3. Epub 2022 Oct 17. PMID: 37006972; PMCID: PMC10064348. 3: Chen J, Guo S, Yu X, Lei J, Xu T, Zhu S, Chen L, Xu P, Zhou X, Yu L. Metabolic interactions between flumatinib and the CYP3A4 inhibitors erythromycin, cyclosporine, and voriconazole. Pharmazie. 2020 Sep 1;75(9):424-429. doi: 10.1691/ph.2020.0068. PMID: 32797767. 4: Jiang L, Yang M. Clinical Efficacy and Safety of Flumatinib in Newly Diagnosed Chronic Myelogenous Leukemia. Pharmazie. 2023 Apr 15;78(1):13-16. doi: 10.1691/ph.2023.2536. PMID: 37138411. 5: Zhao J, Quan H, Xu Y, Kong X, Jin L, Lou L. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25. doi: 10.1111/cas.12320. Epub 2014 Jan 4. PMID: 24205792; PMCID: PMC4317885. 6: Huang SM, Tao T, Wan CL, Wu TM, Cao HY, Qiu Y, Shen XD, Wang BR, Ge SS, Li YY, Zhang TT, Wu B, Xue SL. Flumatinib plus venetoclax as an effective therapy for Philadelphia chromosome-positive acute myeloid leukemia: A case report. Clin Case Rep. 2023 Jan 3;11(1):e6688. doi: 10.1002/ccr3.6688. PMID: 36619491; PMCID: PMC9810787. 7: Zhang Q, Qi L, Ji DX, Li F. [Efficacy and Safety of Flumatinib in Treatment of Patients with Chronic Myeloid Leukemia]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Aug;31(4):1014-1018. Chinese. doi: 10.19746/j.cnki.issn.1009-2137.2023.04.013. PMID: 37551470. 8: Kuang Y, Song HL, Yang GP, Pei Q, Yang XY, Ye L, Yang S, Wu ST, Guo C, He QN, Huang J. Effect of high-fat diet on the pharmacokinetics and safety of flumatinib in healthy Chinese subjects. Cancer Chemother Pharmacol. 2020 Sep;86(3):339-346. doi: 10.1007/s00280-020-04117-w. Epub 2020 Aug 5. PMID: 32757049; PMCID: PMC7479006. 9: Jiang B, Qi J, Sun M, Zheng W, Wei Y, Wang J, Zhang F. Pharmacokinetics of single- and multiple-dose flumatinib in patients with chronic phase chronic myeloid leukemia. Front Oncol. 2023 Feb 6;13:1101738. doi: 10.3389/fonc.2023.1101738. PMID: 36814813; PMCID: PMC9939828. 10: Wang J, Wu J, Wang Y, Zheng B, Wang Y, Jiang C, Zou M, Li H. Basic and clinical study of efficacy and adverse effects of flumatinib in Ph+ ALL. Front Pharmacol. 2023 May 5;14:1178393. doi: 10.3389/fphar.2023.1178393. PMID: 37214433; PMCID: PMC10196016. 11: Liu YN, Xu X, Nie J, Hu Y, Xu X, Xu RA, Du X. Studies on the inhibitory effect of isavuconazole on flumatinib metabolism in vitro and in vivo. Front Pharmacol. 2023 May 4;14:1168852. doi: 10.3389/fphar.2023.1168852. PMID: 37214442; PMCID: PMC10192561. 12: Gong A, Chen X, Deng P, Zhong D. Metabolism of flumatinib, a novel antineoplastic tyrosine kinase inhibitor, in chronic myelogenous leukemia patients. Drug Metab Dispos. 2010 Aug;38(8):1328-40. doi: 10.1124/dmd.110.032326. Epub 2010 May 17. PMID: 20478851. 13: Chen L, Zhang J, Yang N, Tan N, Meng D, Zhang F, Qi Y, Wu G, Li Z. A Unique Three-Way Variant Philadelphia Chromosome t(6;9;22)(p21.3;q34;q11.2) in a Newly Diagnosed Patient with Chronic Myeloid Leukemia Responded to Flumatinib. Onco Targets Ther. 2022 Sep 20;15:1033-1037. doi: 10.2147/OTT.S377342. PMID: 36164408; PMCID: PMC9509008. 14: Lian XY, Dai HP, Cui QY, Tang XW. [Clinical observation of flumatinib combined with induction chemotherapy and sequential allogeneic hematopoietic stem cell transplantation in the treatment of 6 patients with newly diagnosed Ph(+) acute lymphocytic leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2023 Feb 14;44(2):169-172. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2023.02.017. PMID: 36948876; PMCID: PMC10033262. 15: Yang Y, Liu K, Zhong D, Chen X. Simultaneous determination of flumatinib and its two major metabolites in plasma of chronic myelogenous leukemia patients by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 May 1;895-896:25-30. doi: 10.1016/j.jchromb.2012.03.008. Epub 2012 Mar 15. PMID: 22472641. 16: Mi RH, Chen L, Yang HP, Wei XL, Liu J, Yin QS, Zhang LN, Wei XD. [Clinical efficacy and safety of flumatinib combined with multidrug chemotherapy in the treatment of 12 cases with Ph(+) acute lymphoblastic leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2021 Oct 14;42(10):858-861. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2021.10.011. PMID: 34788927; PMCID: PMC8607012. 17: Chang MX, Ma YP. [Effect of flumatinib mesylate on C-MYC, HIF-1α and VEGF in U226 line]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Dec;21(6):1496-500. Chinese. doi: 10.7534/j.issn.1009-2137.2013.06.024. PMID: 24370036. 18: Xu XL, Cao YJ, Zhang W, Rao GW. Research Status, Synthesis and Clinical Application of Recently Marketed and Clinical BCR-ABL Inhibitors. Curr Med Chem. 2022;29(17):3050-3078. doi: 10.2174/0929867328666211012093423. PMID: 34636293. 19: Zhang XS, Liu BC, Du X, Zhang YL, Xu N, Liu XL, Li WM, Lin H, Liang R, Chen CY, Huang J, Yang YF, Zhu HL, Pan L, Wang XD, Li GH, Liu ZG, Zhang YQ, Liu ZF, Hu JD, Liu CS, Li F, Yang W, Meng L, Han YQ, Lin LE, Zhao ZY, Tu CQ, Zheng CF, Bai YL, Zhou ZP, Chen SN, Qiu HY, Yang LJ, Sun XL, Sun H, Zhou L, Liu ZL, Wang DY, Guo JX, Pang LP, Zeng QS, Suo XH, Zhang WH, Zheng YJ, Jiang Q. [To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia]. Zhonghua Xue Ye Xue Za Zhi. 2023 Sep 14;44(9):728-736. Chinese. doi: 10.3760/cma.j.issn.0253-2727.2023.09.005. PMID: 38049316; PMCID: PMC10630575. 20: Singh A, Arkin IT. Targeting Viral Ion Channels: A Promising Strategy to Curb SARS-CoV-2. Pharmaceuticals (Basel). 2022 Mar 24;15(4):396. doi: 10.3390/ph15040396. PMID: 35455392; PMCID: PMC9029588.