9FAI
Human carbonic anhydrase II complexed with 2-hydroselenobenzoic acid
This is a non-PDB format compatible entry.
Summary for 9FAI
| Entry DOI | 10.2210/pdb9fai/pdb |
| Descriptor | Carbonic anhydrase 2, 1,2-ETHANEDIOL, ACETATE ION, ... (6 entities in total) |
| Functional Keywords | carbonic anhydrase, selenol, metalloenzyme, inhibitor, selenoesterase, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29676.66 |
| Authors | Angeli, A.,Ferraroni, M. (deposition date: 2024-05-10, release date: 2025-05-21, Last modification date: 2025-12-03) |
| Primary citation | Lucarini, E.,D'Antogiovanni, V.,Antonioli, L.,Ghelardini, C.,Di Cesare Mannelli, L.,Ferraroni, M.,Locuoco, M.,Capperucci, A.,Tanini, D.,Angeli, A.,Supuran, C.T. Study of Chalcogen Aspirin Derivatives with Carbonic Anhydrase Inhibitory Properties for Treating Inflammatory Pain. Acs Med.Chem.Lett., 15:1559-1565, 2024 Cited by PubMed Abstract: Carbonic anhydrase (CA) inhibitors represent intriguing tools for treating pain. This study aims at studying the pharmacological profile of chalcogen bioisosteres of aspirin, as inhibitors of CA isoforms (hCA I, II, IV, VII, IX, and XII). Our results show that selenoaspirin () displayed markedly superior inhibitory potency across all tested isoforms compared to thioaspirin () and aspirin, with a strong selectivity against the isoform CA IX. X-ray crystallography confirmed that both compounds bind effectively within the active site of hCA II, revealing unique structural characteristics compared to those of aspirin. In a preclinical model of inflammatory pain, compound exhibited a longer lasting antihyperalgesic effect than aspirin, though with a lower potency. Conversely, compound exhibited both lower potency and efficacy than aspirin in reducing pain, which entailed both adverse effects. Nevertheless, the therapeutic potential of chalcogen-based aspirin derivatives as novel CA inhibitors deserves to be further explored for clinical applications. PubMed: 39291024DOI: 10.1021/acsmedchemlett.4c00284 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.272 Å) |
Structure validation
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