3vhc

Hsp90 alpha N-terminal domain in complex with a macrocyclic inhibitorHsp90 alpha N-terminal domain in complex with a macrocyclic inhibitor

Structural highlights 3vhc 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: 3b24, 3b25, 3b26, 3b27, 3b28, 3vha, 3vhd Gene: HSP90AA1 (Homo sapiens) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Macrocyclic compounds bearing a 2-amino-6-arylpyrimidine moiety were identified as potent heat shock protein 90 (Hsp90) inhibitors by modification of 2-amino-6-aryltriazine derivative (CH5015765). We employed a macrocyclic structure as a skeleton of new inhibitors to mimic the geldanamycin-Hsp90 interactions. Among the identified inhibitors, CH5164840 showed high binding affinity for N-terminal Hsp90alpha (K(d)=0.52nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC(50)=0.15muM, NCI-N87 IC(50)=0.066muM). CH5164840 displayed high oral bioavailability in mice (F=70.8%) and potent antitumor efficacy in a HCT116 human colorectal cancer xenograft model (tumor growth inhibition=83%). Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors.,Suda A, Koyano H, Hayase T, Hada K, Kawasaki K, Komiyama S, Hasegawa K, Fukami TA, Sato S, Miura T, Ono N, Yamazaki T, Saitoh R, Shimma N, Shiratori Y, Tsukuda T Bioorg Med Chem Lett. 2012 Jan 15;22(2):1136-41. Epub 2011 Dec 1. PMID:22192591 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Proteins

spinqualitylabelsall models 3vhc, resolution 1.41Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image