Abstract
We succeeded in the design and synthesis of multifunctional chemical probes of the HIF-1alpha inhibitor carboranylphenoxyacetanilide (1) that combine photoaffinity labeling and click reaction to identify the target protein. HSP60 was identified as a primary target protein of 1 using the chemical probes 2 and 3. Furthermore, HSP60 inhibitor 4 suppressed hypoxia-induced HIF activation, indicating that HSP60 affects HIF-1alpha accumulation directly or indirectly.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetanilides / chemical synthesis
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Acetanilides / chemistry
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Acetanilides / pharmacology*
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Boron Compounds / chemical synthesis
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Boron Compounds / chemistry
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Boron Compounds / pharmacology*
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Chaperonin 60 / antagonists & inhibitors*
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Dose-Response Relationship, Drug
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Drug Design
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
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Molecular Probes / chemical synthesis
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Molecular Probes / chemistry
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Molecular Probes / pharmacology*
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Molecular Structure
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Acetanilides
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Boron Compounds
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Chaperonin 60
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Hypoxia-Inducible Factor 1, alpha Subunit
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Molecular Probes