Motesanib

SKU: orb1305790

Description

Motesanib (AMG 706) is an orally administered small molecule inhibitor targeting VEGFR, PDGFR, Kit, and Ret receptor tyrosine kinases. It has been investigated in preclinical cancer research for its anti-angiogenic and anti-proliferative effects, with studies conducted in both in vitro and in vivo models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 453562-69-1
• MW: 373.45
• Purity: 99.09% (May vary between batches)
• Formula: C₂₂H₂₃N₅O
• SMILES: CC1(C)CNc2cc(NC(=O)c3cccnc3NCc3ccncc3)ccc12
• Target: VEGFR,c-Kit
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.36 mM);DMSO:50 mg/mL (133.89 mM)

Bioactivity

• Target IC50:
  c-Kit:8 nM|VEGFR2:3 nM|VEGFR1:2 nM|VEGFR3:6 nM
• In Vivo:
  Motesanib, at a dose of 100 mg/kg, significantly reduces VEGF-induced vascular permeability in a time-dependent manner. When administered orally once or twice daily, it effectively suppresses VEGF-induced angiogenesis in the rat corneal model, with ED50 values of 4.9 mg/kg and 2.1 mg/kg, respectively. Furthermore, Motesanib promotes dose-dependent regression of established A431 xenografts by targeting tumor cell neovascularization. In combination with radiation, it demonstrates pronounced anti-tumor efficacy in head and neck squamous cell carcinoma (HNSCC) xenograft models. Additionally, Motesanib alone, or when combined with docetaxel or tamoxifen, significantly curtails tumor growth and blood vessel density in MCF-7, MDA-MB-231, or Cal-51 xenografts in a dose-dependent manner.
• In Vitro:
  Motesanib exhibits extensive efficacy against the VEGFR family in humans, with more than 1000-fold selectivity over EGFR, Src, and p38 kinase. It notably reduces VEGF-triggered proliferation in HUVECs, achieving an IC50 of 10 nM, but demonstrates minimal influence on bFGF-driven proliferation, with an IC50 exceeding 3,000 nM. Furthermore, Motesanib effectively hinders PDGF-stimulated proliferation and SCF-induced c-kit phosphorylation, presenting IC50 values of 207 nM and 37 nM, respectively. However, it lacks efficacy against EGF-induced EGFR phosphorylation and the viability of A431 cells. While having limited antiproliferative effects on HUVECs growth on its own, Motesanib markedly enhances the sensitivity of these cells to fractionated radiation.
• Cell Research:
  Cells are preincubated for 2 hours with different concentrations of Motesanib, and exposed with 50 ng/mL VEGF or 20 ng/mL bFGF for an additional 72 hours. Cells are washed twice with DPBS, and plates are frozen at -70°C for 24 hours. Proliferation is assessed by the addition of CyQuant dye, and plates are read on a Victor 1420 workstation. IC50 data are calculated using the Levenberg-Marquardt algorithm into a four-parameter logistic equatio.

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

AMG 706, AMG-706, AMG706, CD117, cKit, c-Kit, inhibit, Motesanib, Inhibitor, SCFR, VEGFR3, VEGFR1, VEGFR2, VEGFR, Vascular endothelial growth factor receptor

Compound Identifiers

PubChem CID

11667893