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| Preferred IUPAC name N-(3,3-Dimethyl-2,3-dihydro-1H-indol-6-yl)-2-{amino}pyridine-3-carboxamide | |
| Other names AMG 706 | |
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| Properties | |
| Chemical formula | C22H23N5O |
| Molar mass | 373.460 g·mol |
| Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references | |
Motesanib (AMG 706) is an experimental drug candidate originally developed by Amgen but later investigated by the Takeda Pharmaceutical Company. It 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. It is used as the phosphate salt motesanib diphosphate. After clinical trials in thyroid cancer, non-small cell lung cancer, gastrointestinal stromal cancer, colorectal cancer, and breast cancer, the drug was not found to show sufficient efficacy for further development, and development was abandoned by Takeda.
Clinical trials
Motesanib was originally investigated for effectiveness against advanced nonsquamous non-small-cell lung cancer (NSCLC), with Phase II trials indicating an effectiveness comparable to bevacizumab when they were both used in combination with paclitaxel/carboplatin. However a later and more detailed Phase III trial failed to show any benefit for the treatment of NSCLC. A second Phase III trial was started in 2012, which focused on patients from Asian backgrounds (performed on the basis of subgroup analysis) however this also failed to meet its primary endpoint.
The drug has undergone a Phase II evaluation as first-line therapy for breast cancer however this study found no evidence to support further investigation. Phase II testing against persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas was also unsuccessful. Two phase II clinical trials for thyroid cancer showed promising results.
References
- Stafford, edited by Rongshi Li, Jeffrey A. (2009). "Chapter 5. Discovery of Motesanib". Kinase inhibitor drugs. Hoboken, N.J.: Wiley. pp. 113–130. doi:10.1002/9780470524961.ch5. ISBN 978-0-470-27829-1.
{{cite book}}:|first1=has generic name (help)CS1 maint: multiple names: authors list (link) - ^ "Amgen and Takeda's NSCLC Drug Fails in Phase III Study". 30 Mar 2011.
- "Motesanib". AdisInsight. Retrieved 1 February 2017.
- Blumenschein Jr, G. R.; Kabbinavar, F.; Menon, H.; Mok, T. S. K.; Stephenson, J.; Beck, J. T.; Lakshmaiah, K.; Reckamp, K.; Hei, Y.- J.; Kracht, K.; Sun, Y.- N.; Sikorski, R.; Schwartzberg, L. (14 February 2011). "A phase II, multicenter, open-label randomized study of motesanib or bevacizumab in combination with paclitaxel and carboplatin for advanced nonsquamous non-small-cell lung cancer". Annals of Oncology. 22 (9): 2057–2067. doi:10.1093/annonc/mdq731. PMID 21321086.
- Scagliotti, G. V.; Vynnychenko, I.; Park, K.; Ichinose, Y.; Kubota, K.; Blackhall, F.; Pirker, R.; Galiulin, R.; Ciuleanu, T.-E.; Sydorenko, O.; Dediu, M.; Papai-Szekely, Z.; Banaclocha, N. M.; McCoy, S.; Yao, B.; Hei, Y.-j.; Galimi, F.; Spigel, D. R. (2 July 2012). "International, Randomized, Placebo-Controlled, Double-Blind Phase III Study of Motesanib Plus Carboplatin/Paclitaxel in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer: MONET1" (PDF). Journal of Clinical Oncology. 30 (23): 2829–2836. doi:10.1200/JCO.2011.41.4987. hdl:2318/118283. PMID 22753922.
- "Takeda Initiates Phase 3 Trial of Motesanib in Japan and Additional Asian Countries". Takeda Pharmaceutical Company Limited. Retrieved 19 February 2015.
- Kubota, K.; Ichinose, Y.; Scagliotti, G.; Spigel, D.; Kim, J. H.; Shinkai, T.; Takeda, K.; Kim, S.- W.; Hsia, T.- C.; Li, R. K.; Tiangco, B. J.; Yau, S.; Lim, W.- T.; Yao, B.; Hei, Y.- J.; Park, K. (13 January 2014). "Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC): Asian subgroup analysis". Annals of Oncology. 25 (2): 529–536. doi:10.1093/annonc/mdt552. hdl:2318/150328. PMID 24419239.
- "Takeda Announces Phase 3 MONET-A Study Evaluating Motesanib (AMG 706) in Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer Does Not Meet Primary Endpoint". Takeda Pharmaceutical Company Limited. Retrieved 19 February 2015.
- Martin, Miguel; Roche, Henri; Pinter, Tamas; Crown, John; Kennedy, M John; Provencher, Louise; Priou, Frank; Eiermann, Wolfgang; Adrover, Encarna; Lang, Istvan; Ramos, Manuel; Latreille, Jean; Jagiełło-Gruszfeld, Agnieszka; Pienkowski, Tadeusz; Alba, Emilio; Snyder, Raymond; Almel, Sachin; Rolski, Janusz; Munoz, Montserrat; Moroose, Rebecca; Hurvitz, Sara; Baños, Ana; Adewoye, Henry; Hei, Yong-Jiang; Lindsay, Mary-Ann; Rupin, Matthieu; Cabaribere, David; Lemmerick, Yasmin; Mackey, John R (April 2011). "Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a phase 2, randomised, double-blind, placebo-controlled study". The Lancet Oncology. 12 (4): 369–376. doi:10.1016/S1470-2045(11)70037-7. PMID 21429799.
- Schilder, R.J.; Sill, M.W.; Lankes, H.A.; Gold, M.A.; Mannel, R.S.; Modesitt, S.C.; Hanjani, P.; Bonebrake, A.J.; Sood, A.K.; Godwin, A.K.; Hu, W.; Alpaugh, R.K. (April 2013). "A phase II evaluation of motesanib (AMG 706) in the treatment of persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas: A Gynecologic Oncology Group study". Gynecologic Oncology. 129 (1): 86–91. doi:10.1016/j.ygyno.2013.01.006. PMC 3712785. PMID 23321064.
- Motesanib Diphosphate Provides Anticancer Activity Among Patients with Progressive Thyroid Cancer, CancerConnect.com
- Schlumberger, M. J.; Elisei, R.; Bastholt, L.; Wirth, L. J.; Martins, R. G.; Locati, L. D.; Jarzab, B.; Pacini, F.; Daumerie, C.; Droz, J.-P.; Eschenberg, M. J.; Sun, Y.-N.; Juan, T.; Stepan, D. E.; Sherman, S. I. (29 June 2009). "Phase II Study of Safety and Efficacy of Motesanib in Patients With Progressive or Symptomatic, Advanced or Metastatic Medullary Thyroid Cancer". Journal of Clinical Oncology. 27 (23): 3794–3801. doi:10.1200/JCO.2008.18.7815. PMID 19564535.
- Sherman, Steven I.; Wirth, Lori J.; Droz, Jean-Pierre; Hofmann, Michael; Bastholt, Lars; Martins, Renato G.; Licitra, Lisa; Eschenberg, Michael J.; Sun, Yu-Nien; Juan, Todd; Stepan, Daniel E.; Schlumberger, Martin J. (3 July 2008). "Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer". New England Journal of Medicine. 359 (1): 31–42. doi:10.1056/NEJMoa075853. hdl:2318/100325. PMID 18596272.