Abstract
Epacadostat (EPA), a selective indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, has been investigated in vitro as a human (h) Carbonic Anhydrase Inhibitor (CAI). The kinetic data clearly show, for the first time, EPA to be a highly effective and selective inhibitor for the tumor-associated isoforms hCA IX/XII. We report the high resolution X-ray crystal structure of the EPA-hCA II adduct, and assessed its binding mode to CA IX/XII by means of computational techniques. EPA may exert antitumor effects also due to the potent inhibition of the tumor-associated CAs.
MeSH terms
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Carbonic Anhydrase IX / chemistry
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Carbonic Anhydrase IX / drug effects*
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Carbonic Anhydrase Inhibitors / pharmacology*
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Carbonic Anhydrases / chemistry
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Carbonic Anhydrases / drug effects*
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Catalytic Domain
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Crystallography, X-Ray
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Humans
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Hydrogen Bonding
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Molecular Docking Simulation
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Molecular Structure
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Neoplasms / enzymology*
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Oximes / chemistry
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Oximes / pharmacology*
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Polypharmacology*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology*
Substances
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Carbonic Anhydrase Inhibitors
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Oximes
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Sulfonamides
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epacadostat
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Carbonic Anhydrase IX
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Carbonic Anhydrases
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carbonic anhydrase XII