期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 37, 期 1, 页码 930-939出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2022.2053526
关键词
Tail approach; carbonic anhydrase; inhibitor; X-ray crystallography; hypoxic tumour
资金
- King Saud University, Riyadh, Saudi Arabia [RSP-2021/405]
- Italian Ministry for University and Research (Ministero dell'Istruzione, dell'Universita e della Ricerca [MIUR]), grant PRIN [2017XYBP2R]
Human carbonic anhydrase isoforms IX and XII have been confirmed as anticancer targets, with three-tails approach showing higher selectivity against tumor-associated isoforms and demonstrating anti-proliferative effects in various cancer cell lines. X-ray crystallography studies have been conducted to investigate the binding mode of these inhibitors, providing valuable insights for potential cancer treatments.
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 in vitro the viability of colon cancer (HT29), prostate adenocarcinoma (PC3), and breast cancer (ZR75-1) cell lines was evaluated in normoxic (21% O-2) and hypoxic (3% O-2) conditions demonstrating relevant anti-proliferative effects.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据