Identification of Targets of the HIF-1 Inhibitor IDF-11774 Using Alkyne-Conjugated Photoaffinity Probes
DC Field | Value | Language |
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dc.contributor.author | Ban, Hyun Seung | - |
dc.contributor.author | Naik, Ravi | - |
dc.contributor.author | Kim, Hwan Mook | - |
dc.contributor.author | Kim, Bo-Kyung | - |
dc.contributor.author | Lee, Hongsub | - |
dc.contributor.author | Kim, Inhyub | - |
dc.contributor.author | Ahn, Heechul | - |
dc.contributor.author | Jang, Yerin | - |
dc.contributor.author | Jang, Kyusik | - |
dc.contributor.author | Eo, Yumi | - |
dc.contributor.author | Bin Song, Kyung | - |
dc.contributor.author | Lee, Kyeong | - |
dc.contributor.author | Won, Misun | - |
dc.date.available | 2020-02-28T00:45:46Z | - |
dc.date.created | 2020-02-07 | - |
dc.date.issued | 2016-08 | - |
dc.identifier.issn | 1043-1802 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8021 | - |
dc.description.abstract | We developed a hypoxia-inducible factor-1 (HIF-1) inhibitor, IDF-11774, as a clinical candidate for cancer therapy. To understand the mechanism of action of IDF-11774, we attempted to isolate target proteins of IDF-11774 using bioconjugated probes. Multifunctional chemical probes containing sites for click conjugation and photoaffinity labeling were designed and synthesized. After fluorescence and photoaffinity labeling of proteins, two-dimensional electrophoresis (2DE) was performed to isolate specific molecular targets of IDF-11774. Heat shock protein (HSP) 70 was identified as a target protein of IDF-11774. We revealed that IDF-11774 inhibited HSP70 chaperone activity by binding to its allosteric pocket, rather than the ATP-binding site in its nucleotide-binding domain (NBD). Moreover, IDF-11774 reduced the oxygen consumption rate (OCR) and ATP production, thereby increasing intracellular oxygen tension. This result suggests that the inhibition of HSP70 chaperone activity by IDF-11774 suppresses HIF-1 alpha refolding and stimulates HIF-1 alpha degradation. Taken together, these findings indicate that IDF-11774-derived chemical probes successfully identified IDF-11774's target molecule, HSP70, and elucidated the mode of action of IDF-11774 in inhibiting HSP70 chaperone activity and stimulating HIF-1 alpha degradation in cancer cells. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.relation.isPartOf | BIOCONJUGATE CHEMISTRY | - |
dc.subject | SMALL-MOLECULE INHIBITOR | - |
dc.subject | ADENOSINE-DERIVED INHIBITORS | - |
dc.subject | HIGHLY POTENT | - |
dc.subject | DEHYDROGENASE 2 | - |
dc.subject | ACID ANALOGS | - |
dc.subject | HYPOXIA | - |
dc.subject | HSP70 | - |
dc.subject | PROTEIN | - |
dc.subject | CHAPERONES | - |
dc.subject | APOPTOSIS | - |
dc.title | Identification of Targets of the HIF-1 Inhibitor IDF-11774 Using Alkyne-Conjugated Photoaffinity Probes | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000381716200018 | - |
dc.identifier.doi | 10.1021/acs.bioconjchem.6b00305 | - |
dc.identifier.bibliographicCitation | BIOCONJUGATE CHEMISTRY, v.27, no.8, pp.1911 - 1920 | - |
dc.identifier.scopusid | 2-s2.0-84983608525 | - |
dc.citation.endPage | 1920 | - |
dc.citation.startPage | 1911 | - |
dc.citation.title | BIOCONJUGATE CHEMISTRY | - |
dc.citation.volume | 27 | - |
dc.citation.number | 8 | - |
dc.contributor.affiliatedAuthor | Kim, Hwan Mook | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | SMALL-MOLECULE INHIBITOR | - |
dc.subject.keywordPlus | ADENOSINE-DERIVED INHIBITORS | - |
dc.subject.keywordPlus | HIGHLY POTENT | - |
dc.subject.keywordPlus | DEHYDROGENASE 2 | - |
dc.subject.keywordPlus | ACID ANALOGS | - |
dc.subject.keywordPlus | HYPOXIA | - |
dc.subject.keywordPlus | HSP70 | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | CHAPERONES | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalWebOfScienceCategory | Biochemical Research Methods | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Organic | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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