Abstract
Recently, we identified a thiocarbazate that exhibits potent inhibitory activity against human cathepsin L. Since this structure represents a novel chemotype with potential for activity against the entire cysteine protease family, we designed, synthesized, and assayed a series of analogs to probe the mechanism of action, as well as the structural requirements for cathepsin L activity. Molecular docking studies using coordinates of a papain-inhibitor complex as a model for cathepsin L provided useful insights.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Binding Sites
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Cathepsin L
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Cathepsins / antagonists & inhibitors*
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Crystallography, X-Ray
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Cysteine Endopeptidases
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Cysteine Proteinase Inhibitors* / chemical synthesis
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Cysteine Proteinase Inhibitors* / chemistry
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Cysteine Proteinase Inhibitors* / pharmacology
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Dose-Response Relationship, Drug
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Drug Design
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Drug Evaluation, Preclinical
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Humans
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Hydrazines* / chemical synthesis
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Hydrazines* / chemistry
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Hydrazines* / pharmacology
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Inhibitory Concentration 50
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Models, Molecular
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Molecular Structure
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Papain / antagonists & inhibitors
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Papain / chemistry
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Structure-Activity Relationship
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Sulfhydryl Compounds* / chemical synthesis
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Sulfhydryl Compounds* / chemistry
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Sulfhydryl Compounds* / pharmacology
Substances
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Cysteine Proteinase Inhibitors
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Hydrazines
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Sulfhydryl Compounds
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carbazic acid
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Cathepsins
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Cysteine Endopeptidases
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CTSL protein, human
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Cathepsin L
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Papain