8QUF
carbonic anhydrase XII mimic in complex with 2-(3-((N-(4-sulfamoylbenzyl)pyridine-3-sulfonamido)methyl)phenoxy)acetic acid
This is a non-PDB format compatible entry.
Summary for 8QUF
| Entry DOI | 10.2210/pdb8quf/pdb |
| Descriptor | Carbonic anhydrase 2, DIMETHYL SULFOXIDE, ZINC ION, ... (5 entities in total) |
| Functional Keywords | carbonic anhydrase xii mimic, inhibitor, metalloenzyme, sulfonamide, glaucoma, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 30360.47 |
| Authors | Angeli, A.,Ferraroni, M. (deposition date: 2023-10-16, release date: 2024-10-23, Last modification date: 2025-03-26) |
| Primary citation | Angeli, A.,Chelli, I.,Lucarini, L.,Sgambellone, S.,Marri, S.,Villano, S.,Ferraroni, M.,De Luca, V.,Capasso, C.,Carta, F.,Supuran, C.T. Novel Carbonic Anhydrase Inhibitors with Dual-Tail Core Sulfonamide Show Potent and Lasting Effects for Glaucoma Therapy. J.Med.Chem., 67:3066-3089, 2024 Cited by PubMed Abstract: Glaucoma, a leading cause of irreversible vision loss worldwide, is characterized by elevated intraocular pressure (IOP), a well-established risk factor across all its forms. We present the design and synthesis of 39 novel carbonic anhydrase inhibitors by a dual-tailed approach, strategically crafted to interact with distinct hydrophobic and hydrophilic pockets of CA active sites. The series was investigated against the CA isoforms implicated in glaucoma (hCA II, hCA IV, and hCA XII), and the X-ray crystal structures of compounds , , and with CA II, along with in complex with a hCA XII mimic, were determined. Selected compounds (, , and ) underwent evaluation for their ability to reduce IOP in rabbits with ocular hypertension. Derivative showed significant potency and sustained IOP-lowering effects, surpassing the efficacy of the drugs dorzolamide and bimatoprost. This positions compound as a promising candidate for the development of a novel anti-glaucoma medication. PubMed: 38266245DOI: 10.1021/acs.jmedchem.3c02254 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.141 Å) |
Structure validation
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