Motesanib, Diphosphate Salt

Motesanib, Diphosphate Salt - Names and Identifiers

Name	Motesanib Diphosphate (AMG-706)
Synonyms	AMG706 AMG-706 AMG 706 AMG-706 Unii-T6Q3060U91 Motesanib(AMG-706) Motesanib diphosphate Motesanib, Diphosphate Salt Motesanib diphosphate [usan] Motesanib Diphosphate (AMG-706) N-(2,3-Dihydro-3,3-dimethyl-1H-indol-6-yl)-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide diphosphate
CAS	857876-30-3

Motesanib, Diphosphate Salt - Physico-chemical Properties

Molecular Formula	C22H29N5O9P2
Molar Mass	569.441282
Solubility	Soluble in DMSO (100 mg/ml at 25 °C), water (100 mg/ml at 25 °C), and ethanol (<1 m
Storage Condition	Inert atmosphere,Store in freezer, under -20°C
Use	An ATP-competitive inhibitor.
In vitro study	Motesanib Diphosphate has a broad spectrum of activity in the human VEGFR family, with a selectivity of> 1000 for EGFR, Src, and p38 kinases. Consistent with selectivity, Motesanib Diphosphate significantly inhibited VEGF-induced HUVECs cell proliferation with an IC50 of 10 nM, whereas it had no effect on bFGF-induced proliferation with an IC50 of> 3,000 nM. Motesanib Diphosphate also effectively inhibited PDGF-induced proliferation and SCF-induced c-kit phosphorylation, with IC50 of 207 nM and 37 nM, respectively, but had no effect on EGFR phosphorylation and A431 cell activity induced by EGF. Although it does not have antiproliferative activity on HUVECs, Motesanib Diphosphate sensitizes cells to radioactivity.
In vivo study	Motesanib Diphosphate at a dose of 100 mg/kg significantly inhibited vascular permeability induced by VEGF in a time-dependent manner. Motesanib Diphosphate, administered orally twice or once a day in a rat corneal model, effectively inhibited VEGF-induced angiogenesis in a dose-dependent manner, with ED50 of 2.1 mg/kg and 4.9 mg/kg, respectively. Motesanib Diphosphate acts on tumor cells in a dose-dependent manner by selectively targeting angiogenesis to decline A431 xenografts. Treatment of MCF-7, MDA-MB-231, or Cal-51 xenograft tumors with Motesanib Diphosphate significantly reduced tumor growth and vascular density in a dose-dependent manner, while the effects were significantly enhanced when combined with Docetaxel or Tamoxifen. Motesanib Diphosphate and radiation together act on head and neck squamous cell carcinoma (HNSCC) xenograft models with significant anticancer activity.

Motesanib, Diphosphate Salt - Introduction

Motesanib Diphosphate (AMG-706) is a potent ATP-competitive VEGFR1/2/3 inhibitor with IC50 of 2 nM/3 nM/6 nM, respectively; it has similar inhibitory activity on Kit, and its selectivity to VEGFR is 10 times higher than that of PDGFR and Ret.

Last Update：2022-10-16 17:41:51