7SUW

Carbonic Anhydrase IX-mimic with 2-((3-Aminopropyl)(phenethyl)amino)-N-(furan-2-ylmethyl)-N-(4-sulfamoylphenethyl)acetamide

7SUW の概要

• エントリーDOI: 10.2210/pdb7suw/pdb
• 分子名称: Carbonic anhydrase 2, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ZINC ION, ... (5 entities in total)
• 機能のキーワード: inhibitor, carbonic anhydrase, metal binding protein, lyase-inhibitor complex, lyase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29545.62

構造登録者

McKenna, R.,Combs, J.E. (登録日: 2021-11-18, 公開日: 2022-04-06, 最終更新日: 2023-10-18)

主引用文献

Bonardi, A.,Bua, S.,Combs, J.,Lomelino, C.,Andring, J.,Osman, S.M.,Toti, A.,Di Cesare Mannelli, L.,Gratteri, P.,Ghelardini, C.,McKenna, R.,Nocentini, A.,Supuran, C.T.
The three-tails approach as a new strategy to improve selectivity of action of sulphonamide inhibitors against tumour-associated carbonic anhydrase IX and XII.
J Enzyme Inhib Med Chem, 37:930-939, 2022

PubMed Abstract: Human (h) carbonic anhydrase (CAs, EC 4.2.1.1) isoforms IX and XII were recently confirmed as anticancer targets against solid hypoxic tumours. The "three-tails approach" has been proposed as an extension of the forerunner "tail" and "dual-tail approach" to fully exploit the amino acid differences at the medium/outer active site rims among different hCAs and to obtain more isoform-selective inhibitors. Many three-tailed inhibitors (TTIs) showed higher selectivity against the tumour-associated isoforms hCA IX and XII with respect to the off-targets hCA I and II. X-ray crystallography studies were performed to investigate the binding mode of four TTIs in complex with a hCA IX mimic. The ability of the most potent and selective TTIs to reduce the viability of colon cancer (HT29), prostate adenocarcinoma (PC3), and breast cancer (ZR75-1) cell lines was evaluated in normoxic (21% O) and hypoxic (3% O) conditions demonstrating relevant anti-proliferative effects.

PubMed: 35306936
DOI: 10.1080/14756366.2022.2053526

実験手法

X-RAY DIFFRACTION (1.456 Å)