Abstract
Heat shock protein 90 (Hsp90) plays a key role in stress response and protection of the cell against the effects of mutation. Herein we report the identification of an Hsp90 inhibitor identified by fragment screening using a high-concentration biochemical assay, as well as its optimisation by in silico searching coupled with a structure-based drug design (SBDD) approach.
MeSH terms
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Binding Sites
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Cell Line, Tumor
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Computer Simulation
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Crystallography, X-Ray
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Drug Design
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HSP90 Heat-Shock Proteins / antagonists & inhibitors*
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HSP90 Heat-Shock Proteins / metabolism
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Humans
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Oximes / chemical synthesis
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Oximes / chemistry*
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Oximes / pharmacology
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry*
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Pyrimidines / pharmacology
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Structure-Activity Relationship
Substances
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HSP90 Heat-Shock Proteins
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Oximes
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Pyrimidines