| Literature DB >> 24900240 |
Meizhong Jin1, Prafulla C Gokhale2, Andy Cooke2, Kenneth Foreman1, Elizabeth Buck1, Earl W May1, Lixin Feng2, Mark A Bittner2, Mridula Kadalbajoo1, Darla Landfair2, Kam W Siu1, Kathryn M Stolz1, Douglas S Werner1, Radoslaw S Laufer1, An-Hu Li1, Hanqing Dong1, Arno G Steinig1, Andrew Kleinberg1, Yan Yao1, Jonathan A Pachter1, Robert Wild2, Mark J Mulvihill1.
Abstract
This report describes the investigation of a series of 5,7-disubstituted imidazo[5,1-f][1,2,4]triazine inhibitors of insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (IR). Structure-activity relationship exploration and optimization leading to the identification, characterization, and pharmacological activity of compound 9b, a potent, selective, well-tolerated, and orally bioavailable dual inhibitor of IGF-1R and IR with in vivo efficacy in tumor xenograft models, is discussed.Entities:
Keywords: Insulin-like growth factor-1 receptor (IGF-1R); cancer; inhibitors, structure-based drug design (SBDD); insulin receptor (IR)
Year: 2010 PMID： 24900240 PMCID： PMC4007908 DOI： 10.1021/ml100178g
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.345