| 词条 | Motesanib |
| 释义 |
| ImageFile = Motesanib.svg | ImageSize = 200px | IUPACName = N-(3,3-Dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)amino]pyridine-3-carboxamide | OtherNames = AMG 706 |Section1={{Chembox Identifiers | UNII_Ref = {{fdacite|correct|FDA}} | UNII = U1JK633AYI | IUPHAR_ligand = 5660 | CASNo = 453562-69-1 | CASNo_Ref = {{cascite|correct|CAS}} | ChEMBL = 572881 | PubChem = 11667893 | ChemSpiderID = 9842625 | SMILES = O=C(c2cccnc2NCc1ccncc1)Nc3ccc4c(c3)NCC4(C)C | InChI = 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/h3-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28) |Section2={{Chembox Properties | C=22 | H=23 | N=5 | O=1 | Appearance = | Density = | MeltingPt = | BoilingPt = | Solubility = |Section3={{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }}Motesanib (AMG 706) is an experimental drug candidate originally developed by Amgen[1] 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.[2] 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.[3] Clinical trialsMotesanib 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.[4] However a later and more detailed Phase III trial failed to show any benefit for the treatment of NSCLC.[2][5] A second Phase III trial was started in 2012,[6] which focused on patients from Asian backgrounds (performed on the bases of subgroup analysis)[7] however this also failed to meet its primary endpoint.[8] The drug has undergone a Phase II evaluation as first-line therapy for breast cancer[2] however this study found no evidence to support further investigation.[9] Phase II testing against persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas was also unsuccessful.[10] Two phase II clinical trials for thyroid cancer showed promising results.[11][12][13] References1. ^{{cite book|last1=Stafford|first1=edited by Rongshi Li, Jeffrey A.|title=Kinase inhibitor drugs|date=2009|publisher=Wiley|location=Hoboken, N.J.|isbn=978-0-470-27829-1|pages=113–130|chapter=Chapter 5. Discovery of Motesanib|doi=10.1002/9780470524961.ch5}} 2. ^1 2 {{cite news |url=http://www.genengnews.com/gen-news-highlights/amgen-and-takeda-s-nsclc-drug-fails-in-phase-iii-study/81244902/ |title=Amgen and Takeda’s NSCLC Drug Fails in Phase III Study |date=30 Mar 2011 }} 3. ^{{cite web|title=Motesanib|url=http://adisinsight.springer.com/drugs/800011016|website=AdisInsight|accessdate=1 February 2017}} 4. ^{{cite journal|last1=Blumenschein Jr|first1=G. R.|last2=Kabbinavar|first2=F.|last3=Menon|first3=H.|last4=Mok|first4=T. S. K.|last5=Stephenson|first5=J.|last6=Beck|first6=J. T.|last7=Lakshmaiah|first7=K.|last8=Reckamp|first8=K.|last9=Hei|first9=Y.- J.|last10=Kracht|first10=K.|last11=Sun|first11=Y.- N.|last12=Sikorski|first12=R.|last13=Schwartzberg|first13=L.|title=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|journal=Annals of Oncology|date=14 February 2011|volume=22|issue=9|pages=2057–2067|doi=10.1093/annonc/mdq731|pmid=21321086}} 5. ^{{cite journal|last1=Scagliotti|first1=G. V.|last2=Vynnychenko|first2=I.|last3=Park|first3=K.|last4=Ichinose|first4=Y.|last5=Kubota|first5=K.|last6=Blackhall|first6=F.|last7=Pirker|first7=R.|last8=Galiulin|first8=R.|last9=Ciuleanu|first9=T.-E.|last10=Sydorenko|first10=O.|last11=Dediu|first11=M.|last12=Papai-Szekely|first12=Z.|last13=Banaclocha|first13=N. M.|last14=McCoy|first14=S.|last15=Yao|first15=B.|last16=Hei|first16=Y.-j.|last17=Galimi|first17=F.|last18=Spigel|first18=D. R.|title=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|journal=Journal of Clinical Oncology|date=2 July 2012|volume=30|issue=23|pages=2829–2836|doi=10.1200/JCO.2011.41.4987|pmid=22753922|hdl=2318/118283}} 6. ^{{cite web|title=Takeda Initiates Phase 3 Trial of Motesanib in Japan and Additional Asian Countries|url=http://www.takeda.com/news/2012/20120726_3985.html|publisher=Takeda Pharmaceutical Company Limited|accessdate=19 February 2015}} 7. ^{{cite journal|last1=Kubota|first1=K.|last2=Ichinose|first2=Y.|last3=Scagliotti|first3=G.|last4=Spigel|first4=D.|last5=Kim|first5=J. H.|last6=Shinkai|first6=T.|last7=Takeda|first7=K.|last8=Kim|first8=S.- W.|last9=Hsia|first9=T.- C.|last10=Li|first10=R. K.|last11=Tiangco|first11=B. J.|last12=Yau|first12=S.|last13=Lim|first13=W.- T.|last14=Yao|first14=B.|last15=Hei|first15=Y.- J.|last16=Park|first16=K.|title=Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC): Asian subgroup analysis|journal=Annals of Oncology|date=13 January 2014|volume=25|issue=2|pages=529–536|doi=10.1093/annonc/mdt552|pmid=24419239}} 8. ^{{cite web|title=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|url=http://www.takeda.com/news/2015/20150217_6909.html|publisher=Takeda Pharmaceutical Company Limited|accessdate=19 February 2015}} 9. ^{{cite journal|last1=Martin|first1=Miguel|last2=Roche|first2=Henri|last3=Pinter|first3=Tamas|last4=Crown|first4=John|last5=Kennedy|first5=M John|last6=Provencher|first6=Louise|last7=Priou|first7=Frank|last8=Eiermann|first8=Wolfgang|last9=Adrover|first9=Encarna|last10=Lang|first10=Istvan|last11=Ramos|first11=Manuel|last12=Latreille|first12=Jean|last13=Jagiełło-Gruszfeld|first13=Agnieszka|last14=Pienkowski|first14=Tadeusz|last15=Alba|first15=Emilio|last16=Snyder|first16=Raymond|last17=Almel|first17=Sachin|last18=Rolski|first18=Janusz|last19=Munoz|first19=Montserrat|last20=Moroose|first20=Rebecca|last21=Hurvitz|first21=Sara|last22=Baños|first22=Ana|last23=Adewoye|first23=Henry|last24=Hei|first24=Yong-Jiang|last25=Lindsay|first25=Mary-Ann|last26=Rupin|first26=Matthieu|last27=Cabaribere|first27=David|last28=Lemmerick|first28=Yasmin|last29=Mackey|first29=John R|title=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|journal=The Lancet Oncology|date=April 2011|volume=12|issue=4|pages=369–376|doi=10.1016/S1470-2045(11)70037-7|pmid=21429799}} 10. ^{{cite journal|last1=Schilder|first1=R.J.|last2=Sill|first2=M.W.|last3=Lankes|first3=H.A.|last4=Gold|first4=M.A.|last5=Mannel|first5=R.S.|last6=Modesitt|first6=S.C.|last7=Hanjani|first7=P.|last8=Bonebrake|first8=A.J.|last9=Sood|first9=A.K.|last10=Godwin|first10=A.K.|last11=Hu|first11=W.|last12=Alpaugh|first12=R.K.|title=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|journal=Gynecologic Oncology|date=April 2013|volume=129|issue=1|pages=86–91|doi=10.1016/j.ygyno.2013.01.006|pmid=23321064|pmc=3712785}} 11. ^Motesanib Diphosphate Provides Anticancer Activity Among Patients with Progressive Thyroid Cancer, CancerConnect.com 12. ^{{cite journal|last1=Schlumberger|first1=M. J.|last2=Elisei|first2=R.|last3=Bastholt|first3=L.|last4=Wirth|first4=L. J.|last5=Martins|first5=R. G.|last6=Locati|first6=L. D.|last7=Jarzab|first7=B.|last8=Pacini|first8=F.|last9=Daumerie|first9=C.|last10=Droz|first10=J.-P.|last11=Eschenberg|first11=M. J.|last12=Sun|first12=Y.-N.|last13=Juan|first13=T.|last14=Stepan|first14=D. E.|last15=Sherman|first15=S. I.|title=Phase II Study of Safety and Efficacy of Motesanib in Patients With Progressive or Symptomatic, Advanced or Metastatic Medullary Thyroid Cancer|journal=Journal of Clinical Oncology|date=29 June 2009|volume=27|issue=23|pages=3794–3801|doi=10.1200/JCO.2008.18.7815|pmid=19564535}} 13. ^{{cite journal|last1=Sherman|first1=Steven I.|last2=Wirth|first2=Lori J.|last3=Droz|first3=Jean-Pierre|last4=Hofmann|first4=Michael|last5=Bastholt|first5=Lars|last6=Martins|first6=Renato G.|last7=Licitra|first7=Lisa|last8=Eschenberg|first8=Michael J.|last9=Sun|first9=Yu-Nien|last10=Juan|first10=Todd|last11=Stepan|first11=Daniel E.|last12=Schlumberger|first12=Martin J.|title=Motesanib Diphosphate in Progressive Differentiated Thyroid Cancer|journal=New England Journal of Medicine|date=3 July 2008|volume=359|issue=1|pages=31–42|doi=10.1056/NEJMoa075853|pmid=18596272|hdl=2318/100325}} External links
5 : Tyrosine kinase inhibitors|Nicotinamides|Abandoned drugs|Indolines|Takeda Pharmaceutical Company |
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