WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201072
CAS#: 928037-13-2
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.
MedKoo Cat#: 201072
Name: Golvatinib
CAS#: 928037-13-2
Chemical Formula: C33H37F2N7O4
Exact Mass: 633.28751
Molecular Weight: 633.69
Elemental 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
Appearance: white 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
| Biological target: | Golvatinib (E-7050) is a potent dual inhibitor of both c-Met and VEGFR2 kinases with IC50s of 14 and 16 nM, respectively. |
| In vitro activity: | The new Met-TKI, E7050, reversed 3 HGF-induced resistance mechanisms in EGFR mutant lung cancer. First, E7050 reversed HGF-induced gefitinib resistance by inhibiting Met phosphorylation and thereby suppressing the downstream PI3K/Akt pathway. Second, E7050 inhibited the HGF-induced resistance to next-generation EGFR-TKIs, irreversible EGFR-TKIs, and mutant-selective EGFR-TKIs. Third, E7050 prevented the emergence of resistant clones induced by continuous exposure to HGF. Reference: Clin Cancer Res. 2012 Mar 15;18(6):1663-71. https://clincancerres.aacrjournals.org/content/18/6/1663.long |
| In vivo activity: | Daily oral administration of E7050 inhibited the growth of all tumors in a dose-dependent manner (Fig. 2). High doses of E7050 caused drastic tumor regression, with 2/5 Hs746T tumors failing to re-grow after E7050 treatment (50 mg/kg) was terminated for 20 days and 5/5 failing to re-grow after 100 mg/kg E7050 treatment (data not shown). As a result, tumor-bearing mice were cured by treatment with E7050. During the treatment with E7050, no other macroscopic changes or loss of body weight were observed (data not shown). Reference: Cancer Sci. 2010 Jan;101(1):210-5. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1349-7006.2009.01343.x |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 35.0 | 55.23 |
The following data is based on the product molecular weight 633.69 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. Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res. 2012 Mar 15;18(6):1663-71. doi: 10.1158/1078-0432.CCR-11-1171. Epub 2012 Feb 8. PMID: 22317763. 3. Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res. 2012 Mar 15;18(6):1663-71. doi: 10.1158/1078-0432.CCR-11-1171. Epub 2012 Feb 8. PMID: 22317763. 4. Nakagawa T, Tohyama O, Yamaguchi A, Matsushima T, Takahashi K, Funasaka S, Shirotori S, Asada M, Obaishi H. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5. doi: 10.1111/j.1349-7006.2009.01343.x. Epub 2009 Sep 2. PMID: 19832844. |
| In vitro protocol: | 1. Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res. 2012 Mar 15;18(6):1663-71. doi: 10.1158/1078-0432.CCR-11-1171. Epub 2012 Feb 8. PMID: 22317763. |
| In vivo protocol: | 1. Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res. 2012 Mar 15;18(6):1663-71. doi: 10.1158/1078-0432.CCR-11-1171. Epub 2012 Feb 8. PMID: 22317763. 2. Nakagawa T, Tohyama O, Yamaguchi A, Matsushima T, Takahashi K, Funasaka S, Shirotori S, Asada M, Obaishi H. E7050: a dual c-Met and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5. doi: 10.1111/j.1349-7006.2009.01343.x. Epub 2009 Sep 2. PMID: 19832844. |
1: Nakagawa T, Takeuchi S, Yamada T, Nanjo S, Ishikawa D, Sano T, Kita K, Nakamura T, Matsumoto K, Suda K, Mitsudomi T, Sekido Y, Uenaka T, Yano S. Combined Therapy with Mutant-Selective EGFR Inhibitor and Met Kinase Inhibitor for Overcoming Erlotinib Resistance in EGFR-Mutant Lung Cancer. Mol Cancer Ther. 2012 Oct;11(10):2149-57. doi: 10.1158/1535-7163.MCT-12-0195. Epub 2012 Jul 25. 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, Yano S. Dual inhibition of Met kinase and angiogenesis to overcome HGF-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 2012 Jul 9. PubMed PMID: 22789825.
3: Wang W, Li Q, Takeuchi S, Yamada T, Koizumi H, Nakamura T, Matsumoto K, Mukaida N, Nishioka Y, Sone S, Nakagawa T, Uenaka T, Yano S. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer. Clin Cancer Res. 2012 Mar 15;18(6):1663-71. Epub 2012 Feb 8. PubMed PMID: 22317763.
4: Green DR. 'Tit-for-tat' in cell biology. Nat Rev Mol Cell Biol. 2011 Feb;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 and VEGFR-2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models. Cancer Sci. 2010 Jan;101(1):210-5. Epub 2009 Sep 2. PubMed PMID: 19832844.
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:
)
