8R2F
human carbonic anhydrase II in complex with 4-(((dimethoxyphosphoryl)(4-((dimethoxyphosphoryl)((4-sulfamoylphenyl)amino)methyl)phenyl)methyl)amino)phenyl sulfuramidite
This is a non-PDB format compatible entry.
Summary for 8R2F
| Entry DOI | 10.2210/pdb8r2f/pdb |
| Descriptor | Carbonic anhydrase 2, GLYCEROL, 1,2-ETHANEDIOL, ... (6 entities in total) |
| Functional Keywords | human carbonic anhydrase ii; sulfonamide; phosphonate; metalloenzyme; inhibitor, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 30171.24 |
| Authors | Angeli, A.,Ferraroni, M. (deposition date: 2023-11-04, release date: 2024-11-13, Last modification date: 2025-05-28) |
| Primary citation | Sobati, M.,Abdoli, M.,Angeli, A.,Bonardi, A.,Ferraroni, M.,Supuran, C.T.,Zalubovskis, R. Sulfonamide-incorporated bis( alpha-aminophosphonates) as promising carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and X-ray crystallographic studies. Arch Pharm, 357:e2400038-e2400038, 2024 Cited by PubMed Abstract: A novel series of sulfonamide-incorporated bis(α-aminophosphonates) acting as effective carbonic anhydrase (CA, EC 4.2.1.1) inhibitors is reported. The synthesized bivalent ligands were tested against five human (h) isoforms, hCA I, hCA II, hCA VII, hCA IX, and hCA XIII. Such derivatives showed high activity and selectivity against the cancer-related, membrane-bound isoform hCA IX, and among them, compound 5h, tetraisopropyl (1,3-phenylenebis{[(4-sulfamoylphenyl)amino]methylene})bis(phosphonate) showed a K of 15.1 nM, being highly selective against this isoform over all other investigated ones (hCA I/IX = 42; hCA II/IX = 6, hCA VII/IX = 3, hCA XIII/IX = 5). Therefore, compound 5h could be a potential lead for the development of selective anticancer agents. The newly developed sulfonamides were also found effective inhibitors against the cytosolic hCA XIII isoform. Compound 5i displayed the best inhibition against this isoform with a K of 17.2 nM, equal to that of the well-known inhibitor acetazolamide (AAZ), but significantly more selective over all other tested isoforms (hCA I/XIII = 239; hCA II/XIII = 23, hCA VII/XIII = 2, hCA IX/XIII = 3) compared to AAZ. PubMed: 38498884DOI: 10.1002/ardp.202400038 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.25 Å) |
Structure validation
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