Motesanib Diphosphate | HY-10229

Motesanib Diphosphate (AMG 706 Diphosphate) is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50s of 2 nM/3 nM/6 nM, respectively, and has similar activity against Kit, and is approximately 10-fold more selective for VEGFR than PDGFR and Ret.

IC50 & Target:

In Vitro:

Motesanib Diphosphate (AMG 706 Diphosphate) has broad activity against the human VEGFR family, and displays over 1000-fold selectivity against EGFR, Src, and p38 kinase.Motesanib Diphosphate (AMG 706 Diphosphate) significantly inhibits VEGF-induced cellular proliferation of HUVECs with an IC₅₀ of 10 nM, while displaying little effect at bFGF-induced proliferation with an IC₅₀ of >3,000 nM. Motesanib Diphosphate (AMG 706 Diphosphate) also potently inhibits PDGF-induced proliferation and SCF-induced c-kit phosphorylation with IC₅₀ of 207 nM and 37 nM, respectively, but not effective against the EGF-induced EGFR phosphorylation and cell viability of A431 cells. Although displaying little antiproliferative activity on cell growth of HUVECs alone, Motesanib Diphosphate (AMG 706 Diphosphate) treatment significantly sensitizes the cells to fractionated radiation.

In Vivo:

Motesanib Diphosphate (AMG 706 Diphosphate) (100 mg/kg) significantly inhibits VEGF-induced vascular permeability in a time-dependent manner. Oral administration of Motesanib twice daily or once daily potently inhibits, in a dose-dependent manner, VEGF-induced angiogenesis using the rat corneal model with ED₅₀ of 2.1 mg/kg and 4.9 mg/kg, respectively. Motesanib Diphosphate (AMG 706 Diphosphate) induces a dose-dependent tumor regression of established A431 xenografts by selectively targeting neovascularization in tumor cells^[1]. Motesanib Diphosphate (AMG 706 Diphosphate) in combination with radiation displays significant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) xenograft models. Motesanib Diphosphate (AMG 706 Diphosphate) treatment also induces significant dose-dependent reductions in tumor growth and blood vessel density of MCF-7, MDA-MB-231, or Cal-51 xenografts, which can be markedly enhanced when combined with docetaxel or tamoxifen.

Molecular weight:

569.44

Formula:

C₂₂H₂₉N₅O₉P₂

SMILES:

O=C(C1=CC=CN=C1NCC2=CC=NC=C2)NC3=CC(NCC4(C)C)=C4C=C3.O=P(O)(O)O.O=P(O)(O)O

Storage:

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)