Abstract
Testing of an expanded, 800-compound set of analogues of the earlier described Strecker-type α-aminonitriles (selected from publicly available Enamine Ltd. Screening Collection) in thermal shift assay against bovine carbonic anhydrase (bCA) led to further validation of this new class of inhibitors and identification a new, refined chemotype represented by inhibitors with 10-improved potency. [Formula: see text].
Keywords:
Differential scanning fluorimetry; carbonic anhydrase II; protein affinity; thermal shift assay.
MeSH terms
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Animals
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Carbonic Anhydrase II / antagonists & inhibitors*
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Carbonic Anhydrase II / metabolism
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Carbonic Anhydrase Inhibitors / chemical synthesis
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Carbonic Anhydrase Inhibitors / chemistry
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Carbonic Anhydrase Inhibitors / pharmacology*
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Cattle
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical
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Fluorometry
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Humans
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Molecular Structure
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Nitriles / chemical synthesis
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Nitriles / chemistry
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Nitriles / pharmacology*
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Structure-Activity Relationship
Substances
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Carbonic Anhydrase Inhibitors
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Nitriles
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Carbonic Anhydrase II
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CA2 protein, human
Grants and funding
This research was supported by the Russian Federation Government Megagrant 14.W03.031.0025.