Golvatinib

SKU: orb1300700

Description

Golvatinib (E-7050) is an orally active dual inhibitor targeting c-Met and VEGFR-2 tyrosine kinases, showing potential antineoplastic activity by suppressing tumor growth and angiogenesis. It has been investigated in preclinical studies for various cancers, including hepatocellular carcinoma and glioblastoma, in both in vitro and in vivo models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 928037-13-2
• MW: 633.69
• Purity: 99.50% (May vary between batches)
• Formula: C₃₃H₃₇F₂N₇O₄
• SMILES: CN1CCN(CC1)C1CCN(CC1)C(=O)Nc1cc(Oc2ccc(NC(=O)C3(CC3)C(=O)Nc3ccc(F)cc3)c(F)c2)ccn1
• Target: VEGFR,c-Met/HGFR
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:100 mg/mL (157.81 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (6.31 mM)

Bioactivity

• Target IC50:
  VEGFR2:16 nM|c-Met:14 nM
• In Vivo:
  In vivo studies using E7050 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 E7050 (50–200 mg/kg) induces tumor regression and disappearance. In a peritoneal dissemination model, E7050 shows an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. In another xenograft model research, tumors produced by HGF-transfected Ma-1 (Ma-1/HGF) cells are more angiogenic than vector control tumors and shows resistance to ZD1839. E7050 alone inhibits angiogenesis and retards growth of Ma-1/HGF tumors. E7050 combined with ZD1839 induces marked regression of tumor growth.
• In Vitro:
  In vitro studies indicate that E7050 potently inhibits phosphorylation of both c-Met and VEGFR-2. E7050 also potently represses the growth of both c-met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. E7050 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. E7050 also prevents the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF.
• Cell Research:
  Cells (1–3 × 103 cells/100 μL/well) are seeded on 96-well culture plates with various concentrations of E7050 and cultured for 3 days. Then, 10 μL of WST-8 reagent is added to each well, and absorbance is measured at 450 nm compared with a reference measurement at 660 nm using a MTP-500 microplate reader. HUVEC (2 × 103 cells/well) are cultured for 3 days in medium containing HGF (30 ng/mL), VEGF (20 ng/mL), or basic fibroblast growth factor (bFGF) (20 ng/mL) together with serially diluted E7050.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

VEGFR, VEGFR2, Vascular endothelial growth factor receptor, E7050, E-7050, E 7050, c-Met/HGFR, cMet/HGFR, c-Met, cMet, inhibit, Golvatinib, Inhibitor, HGFR

Compound Identifiers

PubChem CID

16118392