6UFD

Carbonic anhydrase 2 with inhibitor (2Z)-3-oxo-N-(4-sulfamoylphenyl)-2-[(thiophen-2-yl)methylidene]butanamide (11g/D7)

Summary for 6UFD

• Entry DOI: 10.2210/pdb6ufd/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: carbonic anhydrase, inhibitor, complex, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 30016.62

Authors

Peat, T.S. (deposition date: 2019-09-24, release date: 2020-08-05, Last modification date: 2023-10-11)

Primary citation

Fares, M.,Eldehna, W.M.,Bua, S.,Lanzi, C.,Lucarini, L.,Masini, E.,Peat, T.S.,Abdel-Aziz, H.A.,Nocentini, A.,Keller, P.A.,Supuran, C.T.
Discovery of Potent Dual-Tailed Benzenesulfonamide Inhibitors of Human Carbonic Anhydrases Implicated in Glaucoma and in Vivo Profiling of Their Intraocular Pressure-Lowering Action.
J.Med.Chem., 63:3317-3326, 2020

PubMed Abstract: The design of three dual-tailed sulfonamide series , , and as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors are presented. All compounds were evaluated for inhibitory action against pharmacologically relevant human CA isoforms I, II, IV, and VII. Compounds emerged as potent CA inhibitors against the four tested isoforms with a significant selectivity to CA II, which is implicated in glaucoma ( in the range 0.36-6.9 nM). X-ray crystallographic analysis of three compounds (, , and ) bound to CA II showed the validity of the adopted drug design strategy as specific moieties within the ligand structure interacted directly with the hydrophobic and hydrophilic halves of the CA II active site. Compounds - and were evaluated for their intraocular pressure-lowering effects in a rabbit model of glaucoma. and showed significant efficacy when compared to the clinically used drug dorzolamide.

PubMed: 32031797
DOI: 10.1021/acs.jmedchem.9b02090

Experimental method

X-RAY DIFFRACTION (1.48 Å)