"目录号: HY-13905

Protein Tyrosine Kinase/RTK-

Flumatinib (HH-GV-678)甲磺酸盐是imatinib的衍生物，为多种激酶抑制剂，对c-Abl，PDGFRβ和c-Kit的IC50为1.2 nM，307.6 nM和2662 nM。

Bcr-Ablc-KitPDGFR

相关产品

Sorafenib-Dasatinib-Nocodazole-Pexidartinib-BIBF 1120-Ponatinib-Sunitinib-Cabozantinib-Nilotinib-Imatinib Mesylate-Pazopanib-Crenolanib-Axitinib-Dovitinib-WP1130-

生物活性

Description

Flumatinib mesylate (HH-GV-678 mesylate), a derivative of imatinib, is a multi-kinase inhibitor with IC50 Values of 1.2 nM, 307.6 nM and 2662 nM for c-Abl, PDGFRβ and c-Kit respectively.IC50 Value: 1.2 nM (c-Abl); 307.6 nM(PDGFRβ); 2662 nM (c-Kit) [1]Target: c-Abl; c-Kit; PDGRFβin vitro: HH-GV-678 can predominantly inhibit the autophosphorylation of Bcr-Abl in K562 cell. In higher concentration, HH-GV-678 can inhibit the phosphorylation of c-Kit in Mo7e cell and the phosphorylation of PDGFR in Swiss3T3 cell, however, HH-GV-678 has no or little effect on other tyrosine kinase including EGFR、KDR、c-Src andHER2 [1]. Flumatinib effectively overcame the drug resistance of certain KIT mutants with activation loop mutations (i.e., D820G, N822K, Y823D, and A829P) [2].in vivo: The purpose of this study was to identify the metabolites of flumatinib in CML patients, with the aim of determining the main metabolic pathways offlumatinib in humans after oral administration. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry revealed 34 metabolites; 7 primary metabolites were confirmed by comparison with synthetic reference standards. The results show that the parent drugflumatinib was the main form recovered in human plasma, urine, and feces. The main metabolites of flumatinib in humans were the products of N-demethylation, N-oxidation, hydroxylation, and amide hydrolysis [3].

Clinical Trial

NCT02511340

Jiangsu Hansoh Pharmaceutical Co., Ltd.

Chronic Myelogenous Leukemia

January 2013

Phase 2

NCT01503502

Jiangsu HengRui Medicine Co., Ltd.

Myelogenous Leukemia, Chronic

August 2011

Phase 2

NCT02204644

Jiangsu Hansoh Pharmaceutical Co., Ltd.

CML, CML-CP,MMR,TKI

June 2014

Phase 3

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References

[1].Luo H, et al. HH-GV-678, a novel selective inhibitor of Bcr-Abl, outperforms imatinib and effectively overrides imatinib resistance. Leukemia. 2010 Oct;24(10):1807-9.

[2].Zhao J, et al. Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2013 Nov 10.

[3].Gong A, et al. Metabolism of flumatinib, a novel antineoplastic tyrosine kinase inhibitor, in chronic myelogenous leukemia patients. Drug Metab Dispos. 2010 Aug;38(8):1328-40.