9IGD

Structure of human Bcl-xL in complex with small molecule inhibitor

これはPDB形式変換不可エントリーです。

9IGD の概要

• エントリーDOI: 10.2210/pdb9igd/pdb
• 関連するPDBエントリー: 9i9e 9IGB 9IGC
• 分子名称: Apoptosis regulator Bcl-2,Bcl-2-like protein 1, 2-[[6-(1,3-benzothiazol-2-ylamino)-5-methyl-pyridazin-3-yl]-methyl-amino]-1,3-thiazole-4-carboxylic acid, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: apoptosis, b-cell lyphoma, bcl-xl, drug design
• 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: 37272.08

構造登録者

Dokurno, P.,Novak, T.,Kotschy, A.,Hubbard, R.E.,Davidson, J.,Murray, J. (登録日: 2025-02-19, 公開日: 2026-06-24, 最終更新日: 2026-07-08)

主引用文献

Timari, M.P.,Paczal, A.,Herner, A.,Molnar, M.,Madarasz, Z.,Nyerges, M.,Bedford, S.T.,Brooks, T.,Davidson, J.,Daniels, Z.,Dodsworth, M.,Dokurno, P.,Murray, J.B.,Parsons, R.,Sanders, E.,Smith, J.,Webb, P.,Whitehead, N.,Hubbard, R.E.,Starck, J.B.,Maragno, A.L.,Le Toumelin-Braizat, G.,Bresson, L.,Rocchetti, F.,Demarles, D.,Colland, F.,Geneste, O.,Kotschy, A.,Novak, T.
Structure-Based Discovery of Potent BCL-XL Inhibitors through Rescaffolding.
J.Med.Chem., 69:14804-14818, 2026

PubMed Abstract: Evasion of apoptosis is a hallmark of cancer. Deregulation of BCL-XL, a member of the BCL-2 family of proteins, has been linked to the development of various tumor types. This study presents the design and synthesis of BCL-XL inhibitors with novel mono- and bicyclic cores. The new structural features were optimized to combine high binding efficiency with the opening of diverse novel vectors for additional modifications. The lead compounds exhibited picomolar affinities and significant cellular potency in the BCL-XL-dependent MOLT-4 cell line, which also translated into marked tumor growth inhibition in a xenograft study. These findings highlight the potential of BCL-XL inhibitors as therapeutic agents in cancer treatment by targeting the apoptotic intrinsic pathway.

PubMed: 42283755
DOI: 10.1021/acs.jmedchem.6c00865

実験手法

X-RAY DIFFRACTION (2.4 Å)