Synonym: AMG 706; AMG706; AMG706; motesanib

IUPAC/Chemical Name: N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4- ylmethyl)amino]pyridine-3-carboxamide

InChi Key: RAHBGWKEPAQNFF-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H23N5O/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/h4-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28)

SMILES Code: O=C(C1=CC=CN=C1NCC2=CC=NC=C2)NC3=CC4=C(C=C3)C(C)(C)CN4

Technical Data

Additional Information

Motesanib is an orally-administered small molecule antagonist of vascular endothelial growth factor receptors 1, 2 and 3 (“VEGFR1-3”), platelet-derived growth factor receptor (“PDGFR”) and stem cell factor receptor (“c-kit”). It is being investigated as a cancer treatment. We are developing this product in collaboration with Takeda.  
   
 

References

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2: Rosen PJ, Sweeney CJ, Park DJ, Beaupre DM, Deng H, Leitch IM, Shubhakar P, Zhu M, Oliner KS, Anderson A, Yee LK. A phase Ib study of AMG 102 in combination with bevacizumab or motesanib in patients with advanced solid tumors. Clin Cancer Res. 2010 May 1;16(9):2677-87. Epub 2010 Apr 20. PubMed PMID: 20406832.

3: Fujisaka Y, Yamada Y, Yamamoto N, Shimizu T, Fujiwara Y, Yamada K, Tamura T, Watanabe H, Sun YN, Bass MB, Seki M. Phase 1 study of the investigational, oral angiogenesis inhibitor motesanib in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2010 Jan 28. [Epub ahead of print] PubMed PMID: 20107802.

4: Keefe SM, Cohen MA, Brose MS. Targeting vascular endothelial growth factor receptor in thyroid cancer: the intracellular and extracellular implications. Clin Cancer Res. 2010 Feb 1;16(3):778-83. Epub 2010 Jan 26. Review. PubMed PMID: 20103668.

5: Blumenschein GR Jr, Reckamp K, Stephenson GJ, O'Rourke T, Gladish G, McGreivy J, Sun YN, Ye Y, Parson M, Sandler A. Phase 1b study of motesanib, an oral angiogenesis inhibitor, in combination with carboplatin/paclitaxel and/or panitumumab for the treatment of advanced non-small cell lung cancer. Clin Cancer Res. 2010 Jan 1;16(1):279-90. Epub 2009 Dec 22. PubMed PMID: 20028752.

6: Sherman SI. Tyrosine kinase inhibitors and the thyroid. Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):713-22. Review. PubMed PMID: 19942148.

7: Sawaki A, Yamada Y, Komatsu Y, Kanda T, Doi T, Koseki M, Baba H, Sun YN, Murakami K, Nishida T. Phase II study of motesanib in Japanese patients with advanced gastrointestinal stromal tumors with prior exposure to imatinib mesylate. Cancer Chemother Pharmacol. 2010 Apr;65(5):961-7. Epub 2009 Aug 19. PubMed PMID: 19690858; PubMed Central PMCID: PMC2824121.

8: Sugawara M, Geffner DL, Martinez D, Hershman JM. Novel treatment of medullary thyroid cancer. Curr Opin Endocrinol Diabetes Obes. 2009 Oct;16(5):367-72. Review. PubMed PMID: 19633548.

9: Schlumberger MJ, Elisei R, Bastholt L, Wirth LJ, Martins RG, Locati LD, Jarzab B, Pacini F, Daumerie C, Droz JP, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Sherman SI. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. 2009 Aug 10;27(23):3794-801. Epub 2009 Jun 29. PubMed PMID: 19564535.

10: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Mar;31(2):107-46. PubMed PMID: 19455266.

11: Li C, Kuchimanchi M, Hickman D, Poppe L, Hayashi M, Zhou Y, Subramanian R, Kumar G, Surapaneni S. In vitro metabolism of the novel, highly selective oral angiogenesis inhibitor motesanib diphosphate in preclinical species and in humans. Drug Metab Dispos. 2009 Jul;37(7):1378-94. Epub 2009 Apr 16. PubMed PMID: 19372226.

12: Malouf G, Baudin E, Soria JC, Schlumberger M. [Advances in the treatment of thyroid cancer in the era of molecularly targeted therapies]. Bull Cancer. 2009 Jan;96(1):95-101. Review. French. PubMed PMID: 19211364.

13: Kiselyov AS, Semenova M, Semenov VV. 3,4-Disubstituted isothiazoles: novel potent inhibitors of VEGF receptors 1 and 2. Bioorg Med Chem Lett. 2009 Feb 15;19(4):1195-8. Epub 2008 Dec 24. PubMed PMID: 19124243.

14: Coxon A, Bush T, Saffran D, Kaufman S, Belmontes B, Rex K, Hughes P, Caenepeel S, Rottman JB, Tasker A, Patel V, Kendall R, Radinsky R, Polverino A. 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. 2009 Jan 1;15(1):110-8. PubMed PMID: 19118038.

15: Diaz-Cano SJ. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med. 2008 Dec 18;359(25):2727; author reply 2727. PubMed PMID: 19092161.

16: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Oct;30(8):643-72. PubMed PMID: 19088949.

17: Lanzi C, Cassinelli G, Nicolini V, Zunino F. Targeting RET for thyroid cancer therapy. Biochem Pharmacol. 2009 Feb 1;77(3):297-309. Epub 2008 Nov 6. PubMed PMID: 19028457.

18: Azad A, Herbertson RA, Pook D, White S, Mitchell PL, Tebbutt NC. Motesanib diphosphate (AMG 706), an oral angiogenesis inhibitor, demonstrates clinical efficacy in advanced thymoma. Acta Oncol. 2009;48(4):619-21. PubMed PMID: 18979266.