6I0J

Crystal structure of human carbonic anhydrase I in complex with the 4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl sulfamate inhibitor

Summary for 6I0J

• Entry DOI: 10.2210/pdb6i0j/pdb
• Descriptor: Carbonic anhydrase 1, ZINC ION, ACETATE ION, ... (6 entities in total)
• Functional Keywords: carbonic anhydrase i, inhibitor, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 59157.10

Authors

Ferraroni, M.,Supuran, C.T.,Bozdag, M.,Chiapponi, D. (deposition date: 2018-10-26, release date: 2019-11-20, Last modification date: 2024-01-24)

Primary citation

Bozdag, M.,Ferraroni, M.,Ward, C.,Carta, F.,Bua, S.,Angeli, A.,Langdon, S.P.,Kunkler, I.H.,Al-Tamimi, A.S.,Supuran, C.T.
Carbonic anhydrase inhibitors based on sorafenib scaffold: Design, synthesis, crystallographic investigation and effects on primary breast cancer cells.
Eur.J.Med.Chem., 182:111600-111600, 2019

PubMed Abstract: Carbonic anhydrase inhibitors (CAIs) of the sulfonamide, sulfamate and coumarin classes bearing the phenylureido tail found in the clinically used drug Sorafenib, a multikinase inhibitor actually used for the management of hepatocellular carcinomas, are reported. All compounds were assayed on human (h) CA isoforms I, II, VII and IX, involved in various pathologies. Among the sulfonamides, several compounds were selective for inhibiting hCA IX, with K values in the low nanomolar ranges (i.e. 0.7-30.2 nM). We explored the binding modes of such compounds by means of X-ray crystallographic studies on isoform hCA I in adduct with one sulfonamide and a sulfamate inhibitor. Antiproliferative properties of some sulfamates on breast tumor cell lines were also investigated.

PubMed: 31419777
DOI: 10.1016/j.ejmech.2019.111600

Experimental method

X-RAY DIFFRACTION (1.35 Å)