Golvatinib

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

Description:Golvatinib, also known as E7050, is an orally bioavailable dual kinase inhibitor of c-Met (hepatocyte growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) tyrosine kinases with potential antineoplastic activity. c-Met/VEGFR kinase inhibitor E7050 binds to and inhibits the activities of both c-Met and VEGFR-2, which may inhibit tumor cell growth and survival of tumor cells that overexpress these receptor tyrosine kinases. c-Met and VEGFR-2 are upregulated in a variety of various tumor cell types and play important roles in tumor cell growth, migration and angiogenesis.

Price and Availability

Golvatinib (or E7050), purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 201072Name: GolvatinibCAS#: 928037-13-2Chemical Formula: C33H37F2N7O4Exact Mass: 633.28751Molecular Weight: 633.69Elemental Analysis:C, 62.55; H, 5.89; F, 6.00; N, 15.47; O, 10.10

Synonym:E7050; E-7050; E 7050; Golvatinib.

IUPAC/Chemical Name:N-(2-fluoro-4-((2-(4-(4-methylpiperazin-1-yl)piperidine-1-carboxamido)pyridin-4-yl)oxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

InChi Key:BWEYRDZIIMFBJR-UHFFFAOYSA-N

InChi Code:InChI=1S/C33H37F2N7O4/c1-39-16-18-40(19-17-39)23-9-14-41(15-10-23)32(45)38-29-21-26(8-13-37-29)46-25-6-7-28(27(35)20-25)42(24-4-2-22(34)3-5-24)31(44)33(11-12-33)30(36)43/h2-8,13,20-21,23H,9-12,14-19H2,1H3,(H2,36,43)(H,37,38,45)

SMILES Code:O=C(C1(C(N)=O)CC1)N(C2=CC=C(OC3=CC(NC(N4CCC(N5CCN(C)CC5)CC4)=O)=NC=C3)C=C2F)C6=CC=C(F)C=C6

Technical Data

Additional Information

E7050 is the first kinase inhibitor with dual action against both c-Met and VEGFR-2. The dual inhibitory activity of E7050 against tumor growth and angiogenesis results in drastic tumor regression and disappearance and also prolongation of lifespan without adverse effects.  E7050 is currently under evaluation in a phase I clinical trial.    ( Cancer Sci . 2010 Jan;101(1):210-5. Epub 2009 Sep 2.).E7050 is the first kinase inhibitor with dual action against both c-Met and VEGFR-2. The dual inhibitory activity of E7050 against tumor growth and angiogenesis results in drastic tumor regression and disappearance and also prolongation of lifespan without adverse effects.  E7050 is currently under evaluation in a phase I clinical trial.    ().      E7050 circumvented resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevented the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. In the in vivo model, E7050 plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells. CONCLUSIONS: A new Met kinase inhibitor, E7050, reverses the three HGF-induced mechanisms of gefitinib resistance, suggesting that E7050 may overcome HGF-induced resistance to gefitinib and next-generation EGFR-TKIs. (source: Clin Cancer Res. 2012 Mar 15;18(6):1663-71. Epub 2012 Feb 8.)E7050 circumvented resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevented the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. In the in vivo model, E7050 plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells. CONCLUSIONS: A new Met kinase inhibitor, E7050, reverses the three HGF-induced mechanisms of gefitinib resistance, suggesting that E7050 may overcome HGF-induced resistance to gefitinib and next-generation EGFR-TKIs. (source:)

References

1: Nakagawa T, Takeuchi S, Yamada T, Nanjo S,Ishikawa D, Sano T, Kita K, Nakamura T, Matsumoto K, Suda K, MitsudomiT, Sekido Y, Uenaka T, Yano S. Combined Therapy with Mutant-SelectiveEGFR Inhibitor and Met Kinase Inhibitor for Overcoming ErlotinibResistance in EGFR-Mutant Lung Cancer. Mol Cancer Ther. 2012Oct;11(10):2149-57. doi: 10.1158/1535-7163.MCT-12-0195. Epub 2012 Jul25. PubMed PMID: 22844075.

2: Takeuchi S, Wang W, Li Q, Yamada T, Kita K, Donev IS, Nakamura T,Matsumoto K, Shimizu E, Nishioka Y, Sone S, Nakagawa T, Uenaka T, YanoS. Dual inhibition of Met kinase and angiogenesis to overcomeHGF-induced EGFR-TKI resistance in EGFR mutant lung cancer. Am J Pathol.2012 Sep;181(3):1034-43. doi: 10.1016/j.ajpath.2012.05.023. Epub 2012Jul 9. PubMed PMID: 22789825.

3: Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, MatsumotoK, Mukaida N, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Metkinase inhibitor E7050 reverses three different mechanisms of hepatocytegrowth factor-induced tyrosine kinase inhibitor resistance in EGFRmutant lung cancer. Clin Cancer Res. 2012 Mar 15;18(6):1663-71. Epub2012 Feb 8. PubMed PMID: 22317763.

4: Green DR. "Tit-for-tat" in cell biology. Nat Rev Mol Cell Biol. 2011Feb;12(2):73. PubMed PMID: 21252991.

5: Nakagawa T, Tohyama O, Yamaguchi A, Matsushima T, Takahashi K,Funasaka S, Shirotori S, Asada M, Obaishi H. E7050: a dual c-Met andVEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongssurvival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5.Epub 2009 Sep 2. PubMed PMID: 19832844.