5VKC

Crystal structure of MCL-1 in complex with a BIM competitive inhibitor

5VKC の概要

• エントリーDOI: 10.2210/pdb5vkc/pdb
• 分子名称: Induced myeloid leukemia cell differentiation protein Mcl-1, 7-(3-{[4-(4-acetylpiperazin-1-yl)phenoxy]methyl}-1,5-dimethyl-1H-pyrazol-4-yl)-3-{3-[(naphthalen-1-yl)oxy]propyl}-1-[(pyridin-3-yl)methyl]-1H-indole-2-carboxylic acid, ZINC ION, ... (4 entities in total)
• 機能のキーワード: mcl-1, signaling protein-inhibitor complex, signaling protein/inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Membrane ; Single-pass membrane protein : Q07820
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 37944.66

構造登録者

Judge, R.A.,Souers, A.J. (登録日: 2017-04-21, 公開日: 2017-05-03, 最終更新日: 2024-03-13)

主引用文献

Bruncko, M.,Wang, L.,Sheppard, G.S.,Phillips, D.C.,Tahir, S.K.,Xue, J.,Erickson, S.,Fidanze, S.,Fry, E.,Hasvold, L.,Jenkins, G.J.,Jin, S.,Judge, R.A.,Kovar, P.J.,Madar, D.,Nimmer, P.,Park, C.,Petros, A.M.,Rosenberg, S.H.,Smith, M.L.,Song, X.,Sun, C.,Tao, Z.F.,Wang, X.,Xiao, Y.,Zhang, H.,Tse, C.,Leverson, J.D.,Elmore, S.W.,Souers, A.J.
Structure-guided design of a series of MCL-1 inhibitors with high affinity and selectivity.
J. Med. Chem., 58:2180-2194, 2015

PubMed Abstract: Myeloid cell leukemia 1 (MCL-1) is a BCL-2 family protein that has been implicated in the progression and survival of multiple tumor types. Herein we report a series of MCL-1 inhibitors that emanated from a high throughput screening (HTS) hit and progressed via iterative cycles of structure-guided design. Advanced compounds from this series exhibited subnanomolar affinity for MCL-1 and excellent selectivity over other BCL-2 family proteins as well as multiple kinases and GPCRs. In a MCL-1 dependent human tumor cell line, administration of compound 30b rapidly induced caspase activation with associated loss in cell viability. The small molecules described herein thus comprise effective tools for studying MCL-1 biology.

PubMed: 25679114
DOI: 10.1021/jm501258m

実験手法

X-RAY DIFFRACTION (2.31 Å)