7SUY
Carbonic Anhydrase IX-mimic Complexed with 2-((3-Aminopropyl)(phenethyl)amino)-N-(4-fluorobenzyl)-N-(4-sulfamoylphenethyl)acetamide
Summary for 7SUY
| Entry DOI | 10.2210/pdb7suy/pdb |
| Descriptor | Carbonic anhydrase 2, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, N-[(furan-2-yl)methyl]-N-[2-(4-sulfamoylphenyl)ethyl]glycinamide, ... (5 entities in total) |
| Functional Keywords | inhibitor, carbonic anhydrase, metal binding protein, lyase-inhibitor complex, lyase/inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29369.41 |
| Authors | Combs, J.E.,McKenna, R. (deposition date: 2021-11-18, release date: 2022-04-06, Last modification date: 2023-10-18) |
| Primary citation | 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 Cited by 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: 35306936DOI: 10.1080/14756366.2022.2053526 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.405 Å) |
Structure validation
Download full validation report
