6fag | pdb_00006fag

Crystal structure of human carbonic anhydrase I in complex with the 1-(2-hydroxy-5-sulfamoylphenyl)-3-(2-methoxyphenyl)urea inhibitor

spinqualitylabelsall models 6fag, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6fag is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EON, GOL, ZN Activity: Carbonate dehydratase, with EC number 4.2.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CAH1_HUMAN] Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea. Publication Abstract from PubMed Herein we report the 2-aminophenol-4-sulfonamide 1 and its ureido derivatives 2-23 as inhibitors of the carbonic anhydrase (CA, EC 4.2.1.1) enzymes as analogues of the hypoxic tumor phase II entering drug SLC-0111. This scaffold may determine preferential rotational isomers to selectively interact within the tumor-associated CAs. Most of the compounds indeed showed in vitro selective inhibition of the tumor associated CA isoforms IX and XII. The most potent derivative within the series was 11 ( KIs of 2.59 and 7.64 nM on hCA IX and XII, respectively), which shares the 4-fluorophenylureido tail with the clinical candidate. We investigated by means of X-ray crystallographic studies the binding modes of three selected compounds of this series to CA I. The evaluation of therapeutic efficacy of compound 11 in an orthotopic, syngeneic model of CA IX-positive breast cancer in vivo showed close matching antitumoral effects and tolerance with SLC-0111. Discovery of 4-Hydroxy-3-(3-(phenylureido)benzenesulfonamides as SLC-0111 Analogues for the Treatment of Hypoxic Tumors Overexpressing Carbonic Anhydrase IX.,Bozdag M, Carta F, Ceruso M, Ferraroni M, McDonald PC, Dedhar S, Supuran CT J Med Chem. 2018 Jul 26;61(14):6328-6338. doi: 10.1021/acs.jmedchem.8b00770. Epub, 2018 Jul 17. PMID:29962205 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carbonic anhydrase 3D structures

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