• Motesanib, also known as AMG-706, is an orally administered multikinase inhibitor that selectively targets VEGF receptors, platelet-derived growth factor receptors, and Kit receptors with IC₅₀ values of 2nM (VEGFR1), 3nM (VEGFR2), 6nM (VEGFR3), 84nM (PDGFR), and 8nM (Kit). It inhibits angiogenesis and tumor growth in tumor xenografts. Polverino, A. et al., “AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts.” Cancer Res. 66: 8715‑8721 (2006).
• Human breast cancer xenograft models were established in athymic nude mice by implanting MCF-7 (luminal), MDA-MB-231 (mesenchymal) tumor fragments, or Cal-51 (mixed/progenitor) tumor cells. Motesanib treatment significantly inhibited the tumor growth dose-dependently and reduced viable tumor fraction and blood vessel density in vivo. However, motesanib did not affect the proliferation of tumor cells in vitro. Coxon, A. et al., “Broad antitumor activity in breast cancer xenografts by motesanib, a highly selective, oral inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and Kit receptors.” Clin. Cancer Res. 15: 110‑118 (2009).
• Motesanib inhibited mutated Kit kinase autophosphorylation. It also suppressed kinase domain mutations conferring imatinib resistance but did not inhibit the imatinib-resistant D816V mutant. Motesanib inhibited the proliferation of Ba/F3 cells expressing Kit mutants. Caenepeel, S. et al., “Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors.” J. Exp. Clin. Cancer Res. 29: 96 (2010).
• Motesanib demonstrated some antitumor activity in a Phase I study. Rosen, L.S. et al., “Safety, pharmacokinetics, and efficacy of AMG 706, an oral multikinase inhibitor, in patients with advanced solid tumors.” J. Clin. Oncol. 25: 2369‑2376 (2007).
• Motesanib inhibited thyroid tumor xenograft growth, possibly by inhibition of angiogenesis and expression of VEGFR2 and Ret on tumor cells. Coxon, A. et al., “Antitumor Activity of Motesanib in a Medullary Thyroid Cancer Model.” J. Endocrinol. Invest. (Mar 21, 2011 - Epub ahead of print).
• In a phase II study, 93 patients who had progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer were treated with motesanib diphosphate. Motesanib diphosphate induced partial responses in these patients. Anticancer responses were demonstrated in 14% of patients. Disease stabilization was shown in 67% of patients. Sherman, S.I. et al., “Motesanib diphosphate in progressive differentiated thyroid cancer.” N. Engl. J. Med. 359: 31‑42 (2008).
• Another CAS number previously assigned to motesanib free base, namely 894356-47-9, has been deleted by CAS and is no longer in use.
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