|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
12
|
|
pubmed:dateCreated |
2011-6-16
|
|
pubmed:abstractText |
c-Met is a transmembrane tyrosine kinase that mediates activation of several signaling pathways implicated in aggressive cancer phenotypes. In recent years, research into this area has highlighted c-Met as an attractive cancer drug target, triggering a number of approaches to disrupt aberrant c-Met signaling. Screening efforts identified a unique class of 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one kinase inhibitors, exemplified by 1. Subsequent SAR studies led to the development of 81 (MK-2461), a potent inhibitor of c-Met that was efficacious in preclinical animal models of tumor suppression. In addition, biochemical studies and X-ray analysis have revealed that this unique class of kinase inhibitors binds preferentially to the activated (phosphorylated) form of the kinase. This report details the development of 81 and provides a description of its unique biochemical properties.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
1520-4804
|
|
pubmed:author |
pubmed-author:AltmanMichael DMD,
pubmed-author:DahlbergWilliam KWK,
pubmed-author:DavisLenoraL,
pubmed-author:DeshmukhSujal VSV,
pubmed-author:DinsmoreChristopher JCJ,
pubmed-author:FalconeDanielleD,
pubmed-author:GabardaAna EAE,
pubmed-author:GuerinDavid JDJ,
pubmed-author:HangGaozhenG,
pubmed-author:HatchHaroldH,
pubmed-author:HolmesRachaelR,
pubmed-author:JewellJames PJP,
pubmed-author:KatzJason DJD,
pubmed-author:KuniiKaikoK,
pubmed-author:LimJongwonJ,
pubmed-author:LumbKevin JKJ,
pubmed-author:LutterbachBartB,
pubmed-author:MarshallC GaryCG,
pubmed-author:MathvinkRobertR,
pubmed-author:NazefNaimN,
pubmed-author:PanBo-ShengBS,
pubmed-author:PatelSangita BSB,
pubmed-author:QuXianluX,
pubmed-author:ReillyJohn FJF,
pubmed-author:RickertKeith WKW,
pubmed-author:RosensteinCraigC,
pubmed-author:SoissonStephen MSM,
pubmed-author:SpencerKerrie BKB,
pubmed-author:SzewczakAlexander AAA,
pubmed-author:WalkerDeborahD,
pubmed-author:WangWenxianW,
pubmed-author:YenPP,
pubmed-author:YoungJonathanJ,
pubmed-author:ZengQinwenQ
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
23
|
|
pubmed:volume |
54
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
4092-108
|
|
pubmed:meshHeading |
pubmed-meshheading:21608528-Animals,
pubmed-meshheading:21608528-Antineoplastic Agents,
pubmed-meshheading:21608528-Benzocycloheptenes,
pubmed-meshheading:21608528-Cell Line, Tumor,
pubmed-meshheading:21608528-Crystallography, X-Ray,
pubmed-meshheading:21608528-Dogs,
pubmed-meshheading:21608528-Drug Screening Assays, Antitumor,
pubmed-meshheading:21608528-Female,
pubmed-meshheading:21608528-Haplorhini,
pubmed-meshheading:21608528-Humans,
pubmed-meshheading:21608528-Mice,
pubmed-meshheading:21608528-Mice, Nude,
pubmed-meshheading:21608528-Models, Molecular,
pubmed-meshheading:21608528-Mutation,
pubmed-meshheading:21608528-Neoplasm Transplantation,
pubmed-meshheading:21608528-Phosphorylation,
pubmed-meshheading:21608528-Protein Binding,
pubmed-meshheading:21608528-Pyrazoles,
pubmed-meshheading:21608528-Pyridines,
pubmed-meshheading:21608528-Rats,
pubmed-meshheading:21608528-Receptor Protein-Tyrosine Kinases,
pubmed-meshheading:21608528-Structure-Activity Relationship,
pubmed-meshheading:21608528-Sulfonamides,
pubmed-meshheading:21608528-Transplantation, Heterologous
|
|
pubmed:year |
2011
|
|
pubmed:articleTitle |
Discovery of a 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (MK-2461) inhibitor of c-Met kinase for the treatment of cancer.
|
|
pubmed:affiliation |
Department of Chemistry, Merck Research Laboratories, 33 Avenue Louis Pasteur, BMB-2-114, Boston, Massachusetts 02115, United States. jason_katz2@merck.com
|
|
pubmed:publicationType |
Journal Article
|
