857876-30-3

Basic information

• Product Name: AMG-706
• Synonyms: AMG-706;Motesanib(AMG-706);Motesanib diphosphate;Motesanib diphosphate [usan];Unii-T6Q3060U91;N-(2,3-Dihydro-3,3-dimethyl-1H-indol-6-yl)-2-[(4-pyridinylmethyl)amino]-3-pyridinecarboxamide diphosphate;Motesanib, Diphosphate Salt;N-(2,3-Dihydro-3,3-diMethyl-1H-indol-6-yl)-2-[(4-pyridinylMethyl)aMino]-3-pyridinecarboxaMide Phosphate
• CAS NO: 857876-30-3
• Molecular Formula: C22H29N5O9P2
• Molecular Weight: 569.441282
• Product Categories: Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Antineoplastic
• Mol File: 857876-30-3.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 858.7 °C at 760 mmHg
• Flash Point: 473.1 °C
• Appearance: /
• Vapor Pressure: 2.04E-31mmHg at 25°C
• Storage Temp.: Inert atmosphere,Store in freezer, under -20°C
• Solubility: ≥28.45 mg/mL in DMSO; insoluble in H2O; ≥3.47 mg/mL in EtOH with ultrasonic
• CAS DataBase Reference: AMG-706(CAS DataBase Reference)
• NIST Chemistry Reference: AMG-706(857876-30-3)
• EPA Substance Registry System: AMG-706(857876-30-3)

Safety Data

• Hazardous Substances Data: 857876-30-3(Hazardous Substances Data)

Usage

Uses

An oral angiogenesis inhibitor, demonstrates clinical efficacy in advanced thymoma.

Biological Activity

motesanib diphosphate is a diphosphate form of motesanib. it is a potent atp-competitive inhibitor of vegfr1/2/3 with ic50 of 2 nm/3 nm/6 nm, respectively [1].vascular endothelial growth factor (vegf) is an important signaling protein involved in both vasculogenesis (the formation of the circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). motesanib (amg 706) is an orally administered small molecule belonging to angiokinase inhibitor class which acts as an antagonist of vegf receptors, platelet-derived growth factor receptors, and stem cell factor receptors.

in vitro

motesanib diphosphate has broad activity against the human vegfr family, and displays >1000 selectivity against egfr, src, and p38 kinase. motesanib 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 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 [1]. althouth displaying little antiproliferative activity on cell growth of huvecs alone, motesanib diphosphate treatment significantly sensitizes the cells to fractionated radiation [2].

in vivo

oral administration of amg 706 potently inhibited vegf-induced angiogenesis in the rat corneal model and induced regression of established a431 xenografts. amg 706 was well tolerated and had no significant effects o amg 706n body weight or on the general health of the animals. histologic analysis of tumor xenografts from amg 706–treated animals revealed an increase in endothelial apoptosis and a reduction in blood vessel area that preceded an increase in tumor cell apoptosis. in summary, amg 706 is an orally bioavailable, well-tolerated multikinase inhibitor that is presently under clinical investigation for the treatment of human malignancies [1].

InChI:InChI=1/C22H23N5O.2H3O4P/c1-22(2)14-26-19-12-16(5-6-18(19)22)27-21(28)17-4-3-9-24-20(17)25-13-15-7-10-23-11-8-15;2*1-5(2,3)4/h3-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28);2*(H3,1,2,3,4)