6VWC

Crystal structure of Bcl-xL in complex with tetrahydroisoquinoline-pyridine based inhibitors

6VWC の概要

• エントリーDOI: 10.2210/pdb6vwc/pdb
• 分子名称: Bcl-2-like protein 1, 6-{8-[(1,3-benzothiazol-2-yl)carbamoyl]-3,4-dihydroisoquinolin-2(1H)-yl}-3-{1-[(pyridin-4-yl)methyl]-1H-pyrazol-4-yl}pyridine-2-carboxylic acid (3 entities in total)
• 機能のキーワード: bcl-xl inhibitor, apoptosis, structure-based drug design, apoptosis-apoptosis inhibitor complex, apoptosis/apoptosis inhibitor
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38554.93

構造登録者

Judge, R.A.,Judd, A.S. (登録日: 2020-02-19, 公開日: 2020-10-21, 最終更新日: 2023-10-11)

主引用文献

Wang, L.,Doherty, G.A.,Judd, A.S.,Tao, Z.F.,Hansen, T.M.,Frey, R.R.,Song, X.,Bruncko, M.,Kunzer, A.R.,Wang, X.,Wendt, M.D.,Flygare, J.A.,Catron, N.D.,Judge, R.A.,Park, C.H.,Shekhar, S.,Phillips, D.C.,Nimmer, P.,Smith, M.L.,Tahir, S.K.,Xiao, Y.,Xue, J.,Zhang, H.,Le, P.N.,Mitten, M.J.,Boghaert, E.R.,Gao, W.,Kovar, P.,Choo, E.F.,Diaz, D.,Fairbrother, W.J.,Elmore, S.W.,Sampath, D.,Leverson, J.D.,Souers, A.J.
Discovery of A-1331852, a First-in-Class, Potent, and Orally-Bioavailable BCL-X L Inhibitor.
Acs Med.Chem.Lett., 11:1829-1836, 2020

PubMed Abstract: Herein we describe the discovery of A-1331852, a first-in-class orally active BCL-X inhibitor that selectively and potently induces apoptosis in BCL-X-dependent tumor cells. This molecule was generated by re-engineering our previously reported BCL-X inhibitor A-1155463 using structure-based drug design. Key design elements included rigidification of the A-1155463 pharmacophore and introduction of sp-rich moieties capable of generating highly productive interactions within the key P4 pocket of BCL-X. A-1331852 has since been used as a critical tool molecule for further exploring BCL-2 family protein biology, while also representing an attractive entry into a drug discovery program.

PubMed: 33062160
DOI: 10.1021/acsmedchemlett.9b00568

実験手法

X-RAY DIFFRACTION (1.604 Å)