3QTF

Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity

3QTF の概要

• エントリーDOI: 10.2210/pdb3qtf/pdb
• 分子名称: Heat shock protein HSP 90-alpha, (6S)-6,15,15,18-tetramethyl-17-oxo-2,3,4,5,6,7,14,15,16,17-decahydro-1H-8,12-(metheno)[1,4,9]triazacyclotetradecino[9,8-a]indole-9-carboxamide, DIMETHYL SULFOXIDE, ... (4 entities in total)
• 機能のキーワード: chaperone, atp binding domain, atp-binding, nucleotide-binding, phosphoprotein, stress response, chaperone-chaperone inhibitor complex, chaperone/chaperone inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P07900
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25899.24

構造登録者

Zapf, C.W.,Bloom, J.D.,McBean, J.L.,Dushin, R.G.,Nittoli, T.,Ingalls, C.,Sutherland, A.G.,Sonye, J.P.,Eid, C.N.,Golas, J.,Liu, H.,Boschelli, F.,Hu, Y.,Vogan, E.M.,Levin, J.I. (登録日: 2011-02-22, 公開日: 2011-04-06, 最終更新日: 2024-02-21)

主引用文献

Zapf, C.W.,Bloom, J.D.,McBean, J.L.,Dushin, R.G.,Nittoli, T.,Ingalls, C.,Sutherland, A.G.,Sonye, J.P.,Eid, C.N.,Golas, J.,Liu, H.,Boschelli, F.,Hu, Y.,Vogan, E.,Levin, J.I.
Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity.
Bioorg.Med.Chem.Lett., 21:2278-2282, 2011

PubMed Abstract: A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. A basic nitrogen within the tether linking the aniline nitrogen atom to a tetrahydroindolone moiety allowed access to compounds with good physical properties. Important structure-activity relationship information was obtained from this series which led to the discovery of a soluble and stable compound which is potent in an Hsp90 binding and cell-proliferation assay.

PubMed: 21420297
DOI: 10.1016/j.bmcl.2011.02.101

実験手法

X-RAY DIFFRACTION (1.5703 Å)