5X9P

Crystal structure of the BCL6 BTB domain in complex with Compound 5

5X9P の概要

• エントリーDOI: 10.2210/pdb5x9p/pdb
• 関連するPDBエントリー: 5X9O
• 分子名称: B-cell lymphoma 6 protein, 3-[[4-chloranyl-2-nitro-5-[(2-oxidanylidene-1,3-dihydrobenzimidazol-5-yl)amino]phenyl]amino]propanoic acid (3 entities in total)
• 機能のキーワード: transcription repressor, transcription-inhibitor complex, transcription/inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : P41182
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16679.50

構造登録者

Sogabe, S.,Ida, K.,Lane, W.,Snell, G. (登録日: 2017-03-08, 公開日: 2017-08-16, 最終更新日: 2023-11-22)

主引用文献

Yasui, T.,Yamamoto, T.,Sakai, N.,Asano, K.,Takai, T.,Yoshitomi, Y.,Davis, M.,Takagi, T.,Sakamoto, K.,Sogabe, S.,Kamada, Y.,Lane, W.,Snell, G.,Iwata, M.,Goto, M.,Inooka, H.,Sakamoto, J.I.,Nakada, Y.,Imaeda, Y.
Discovery of a novel B-cell lymphoma 6 (BCL6)-corepressor interaction inhibitor by utilizing structure-based drug design
Bioorg. Med. Chem., 25:4876-4886, 2017

PubMed Abstract: B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein-protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6-corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer. Starting from high-throughput screening hits 1a and 2a, we identified a novel BCL6-corepressor interaction inhibitor 8c (cell-free enzyme-linked immunosorbent assay [ELISA] IC=0.10µM, cell-based mammalian two-hybrid [M2H] assay IC=0.72µM) by utilizing structure-based drug design (SBDD) based on an X-ray crystal structure of 1a bound to BCL6. Compound 8c also showed a good pharmacokinetic profile, which was acceptable for both in vitro and in vivo studies.

PubMed: 28760529
DOI: 10.1016/j.bmc.2017.07.037

実験手法

X-RAY DIFFRACTION (1.86 Å)