9F2N

Structure of human carbonic anhydrase XII complexed with 3-(cyclooctylamino)-2,6-difluoro-4-((3-hydroxypropyl)sulfonyl)-5-(piperidin-1-yl)benzenesulfonamide

これはPDB形式変換不可エントリーです。

9F2N の概要

• エントリーDOI: 10.2210/pdb9f2n/pdb
• 関連するPDBエントリー: 9F2O 9F30 9F3G
• 分子名称: Carbonic anhydrase 12, ZINC ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: drug design, carbonic anhydrase, benzenesulfonamide, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61323.11

構造登録者

Manakova, E.N.,Grazulis, S.,Paketuryte, V.,Smirnov, A. (登録日: 2024-04-23, 公開日: 2025-05-14, 最終更新日: 2025-09-24)

主引用文献

Vaskevicius, A.,Zvirblis, M.,Kurtenoka, M.,Leitans, J.,Manakova, E.,Paketuryte-Latve, V.,Kvietkauskaite, A.,Kazaks, A.,Eimonta, V.,Cerepenkaite, K.,Kazokaite-Adomaitiene, J.,Mickeviciu̅te, A.,Juozapaitiene, V.,Tars, K.,Grazulis, S.,Matuliene, J.,Dudutiene, V.,Shubin, K.,Matulis, D.,Zubriene, A.
Di- meta -Substituted Fluorinated Benzenesulfonamides as Potent and Selective Anticancer Inhibitors of Carbonic Anhydrase IX and XII.
J.Med.Chem., 68:18389-18406, 2025

PubMed Abstract: The development of selective drug candidate molecules for cancer-related carbonic anhydrase isozymes IX and XII is challenging due to high homology binding sites among 12 catalytically active isozymes. Starting from the trifluorinated benzenesulfonamide with cyclooctylamino substituent at the position, we designed and synthesized di--substituted fluorinated benzenesulfonamides with up to 10-fold affinity improvement for CAIX, resulting in low picomolar binders. The resulting CAIX-targeting compounds showed up to 1000-fold selectivity over off-target CA isozymes. The crystal structures of CAIX and CAXII complexes with synthesized compounds revealed detailed insights into protein-ligand interactions and adopted complex conformation. The potential of compounds with reduced off-target effects as possible anticancer drugs is supported by this study.

PubMed: 40833423
DOI: 10.1021/acs.jmedchem.5c01142

実験手法

X-RAY DIFFRACTION (1.21 Å)