E-7050

SKU: orb1223626

Description

E-7050 (Golvatinib) is a potent, dual c-Met and VEGFR-2 tyrosine kinase inhibitor with IC50 of 14 and 16 nM (kinase phosphorylation inhibition); also strongly inhibits the growth of MKN45, EBC-1, Hs746T, and SNU-5 tumor cells with IC50 values of 37, 6.2, 23, and 24 nM, respectively, selectively inhibits the growth of the c-Met amplified tumor cell lines in vitro; specifically inhibits HGF and VEGF stimulated HUVEC growth with IC50 values of 17 nM and 84 nM respectively, but bFGF stimulated HUVEC; demonstrates inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models.Liver Cancer Phase 2 Discontinued(In Vitro):Golvatinib (E-7050) potently inhibits phosphorylation of both c-Met and VEGFR-2. Golvatinib also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF.Golvatinib strongly inhibits the growth of MKN45, EBC-1, Hs746T, and SNU-5 tumor cells with IC50 values of 37, 6.2, 23, and 24 nM, respectively. The growth of A549, SNU-1 and 0MKN74 tumor cells is inhibited by Golvatinib with much higher IC50 values.Golvatinib circumvents 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.Golvatinib also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF.(In Vivo):Golvatinib (E-7050) shows inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models.Treatment of some tumor lines containing c-met amplifications with high doses of Golvatinib (50-200 mg/kg) induced tumor regression and disappearance. In a peritoneal dissemination model, Golvatinib shows an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice.Golvatinib (E7050) plus Gefitinib results in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells.

Key Properties

• CAS Number: 928037-13-2
• MW: 633.6882
• Purity: >98% (HPLC)
• Formula: C₃₃H₃₇F₂N₇O₄
• SMILES: 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
• Target: c-Met/HGFR
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Golvatinib (E-7050) shows inhibition of the phosphorylation of c-Met and VEGFR-2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models. Treatment of some tumor lines containing c-met amplifications with high doses of Golvatinib (50-200 mg/kg) induced tumor regression and disappearance. In a peritoneal dissemination model, Golvatinib shows an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. Golvatinib (E7050) plus Gefitinib results in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells.
• In Vitro:
  Golvatinib (E-7050) potently inhibits phosphorylation of both c-Met and VEGFR-2. Golvatinib also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. Golvatinib strongly inhibits the growth of MKN45, EBC-1, Hs746T, and SNU-5 tumor cells with IC50 values of 37, 6.2, 23, and 24 nM, respectively. The growth of A549, SNU-1 and 0MKN74 tumor cells is inhibited by Golvatinib with much higher IC50 values. Golvatinib circumvents 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. Golvatinib also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Golvatinib | E7050

Quick Database Links

Gene Symbol

c-Met/HGFR