Identification of HSP60 as a primary target of o-carboranylphenoxyacetanilide, an HIF-1alpha inhibitor.
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.
Ban
Hyun Seung
HS
Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Tokyo 171-8588, Japan.
Shimizu
Kazuki
K
Minegishi
Hidemitsu
H
Nakamura
Hiroyuki
H
D000083:Acetanilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000083:Acetanilides; D001896:Boron Compounds; D018834:Chaperonin 60; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015335:Molecular Probes