Abstract
By using a combination of molecular modeling, combinatorial chemistry, and biological essays, novel scaffold molecules for the inhibition of caspase-3 have been developed. These compounds have an overall attenuated negative charge and show similar IC(50) values for both recombinant and human endogenous caspase-3. This might provide the basis for a novel strategy for the discovery of potent and more druglike inhibitors of caspase-3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Binding Sites / drug effects
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Caspase Inhibitors*
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Cell Line
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Combinatorial Chemistry Techniques
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Drug Design
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Drug Evaluation, Preclinical
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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Hydantoins / chemistry*
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Molecular Conformation
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Peptides / chemical synthesis
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Peptides / chemistry
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Peptides / pharmacology*
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Recombinant Proteins / antagonists & inhibitors
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Caspase Inhibitors
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Enzyme Inhibitors
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Hydantoins
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Peptides
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Recombinant Proteins