Abstract
Epacadostat (EPA), a new and promising anti-cancer small molecule is firmly established as selective inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). The X-Ray structure of the human CA IX mimic in complex with EPA is investigated here for the first time and compared to previously reported EPA-CA II adduct. The structural information obtained are all in agreement with the in vitro kinetic data which accounted for a selective inhibition of the CA IX over the CA II isoform.
Keywords:
Carbonic Anhydrase inhibitor; Carbonic Anhydrases IX; Check point inhibitor; Epacadostat; Metalloenzymes.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / metabolism*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Carbonic Anhydrase IX / antagonists & inhibitors
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Carbonic Anhydrase IX / chemistry
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Carbonic Anhydrase IX / metabolism*
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Carbonic Anhydrase Inhibitors / chemistry*
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Carbonic Anhydrase Inhibitors / pharmacology*
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Crystallography, X-Ray
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Humans
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Molecular Docking Simulation
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Oximes / chemistry*
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Oximes / pharmacology*
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Sulfonamides / chemistry*
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Sulfonamides / pharmacology*
Substances
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Antigens, Neoplasm
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Antineoplastic Agents
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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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CA9 protein, human
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Carbonic Anhydrase IX