3r4m

Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamideOptimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl}-N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxamide

Structural highlights 3r4m is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 3r4n, 3r4o, 3r4p Gene: HSP90AA1, HSP90A, HSPC1, HSPCA (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed A novel class of heat shock protein 90 (Hsp90) inhibitors was discovered by high-throughput screening and was subsequently optimized using a combination of structure-based design, parallel synthesis, and the application of medicinal chemistry principles. Through this process, the biochemical and cell-based potency of the original HTS lead were substantially improved along with the corresponding metabolic stability properties. These efforts culminated with the identification of a development candidate (compound 42) which displayed desired PK/PD relationships, significant efficacy in a melanoma A2058 xenograft tumor model, and attractive DMPK profiles. Optimization of Potent, Selective, and Orally Bioavailable Pyrrolodinopyrimidine-Containing Inhibitors of Heat Shock Protein 90. Identification of Development Candidate 2-Amino-4-{4-chloro-2-[2-(4-fluoro-1H-pyrazol-1-yl)ethoxy]-6-methylphenyl} -N-(2,2-difluoropropyl)-5,7-dihydro-6H-pyrrolo[3,4-d]pyrimidine-6-carboxam ide.,Zehnder L, Bennett M, Meng J, Huang B, Ninkovic S, Wang F, Braganza J, Tatlock J, Jewell T, Zhou JZ, Burke B, Wang J, Maegley K, Mehta PP, Yin MJ, Gajiwala KS, Hickey MJ, Yamazaki S, Smith E, Kang P, Sistla A, Dovalsantos E, Gehring MR, Kania R, Wythes M, Kung PP J Med Chem. 2011 Apr 20. PMID:21438541 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Proteins

spinqualitylabelsall models 3r4m, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image