ReferenceID 390
Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New Class of HSP90 C-Terminal Inhibitors
J Med Chem
Previously, vibsanin B (ViB) was found to preferentially target HSP90β compared to HSP90α. In this study, multiple experiments, including pull-down assays of biotin-ViB with recombinant HSP90β-NTD, MD, CTD, and full-leng
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Record Fields
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- Reference Id
- 390
- Evidence Id
- 16980
- Core Evidence Id
- 16980
- Source Reference Id
- 756
- Herb2 Reference Id
- HBREF001299
- Subject Paper Key
- HBIN047881_29019670
- Pubmed Id
- 29019670
- Doi
- 10.1021/acs.jmedchem.7b01395
- Paper Title
- Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New Class of HSP90 C-Terminal Inhibitors
- Paper Abstract
- Previously, vibsanin B (ViB) was found to preferentially target HSP90β compared to HSP90α. In this study, multiple experiments, including pull-down assays of biotin-ViB with recombinant HSP90β-NTD, MD, CTD, and full-length HSP90β, molecular docking of ViB and its derivatives to the HSP90 CTD, and a inhibition assay of interaction of the HSP90β CTD with GST-tagged cyclophilin 40 (Cyp40) by ViB derivatives, suggest that ViB can directly bind to the HSP90 C-terminus. On the basis of the docking predictions and primary structure-activity relationships (SARs), a series of ViB analogues devised with focus on the C18 position, along with compounds derivatized at the C4, C7, and C8 positions, were designed and chemically synthesized. Compound 12f (IC50 = 1.12 μM against SK-BR-3) exhibits great potency with drug-like properties. Overall, our findings demonstrate that compounds with the vibsanin B scaffold are a new class of HSP90 C-terminal inhibitors with considerable potential as anticancer agents.
- Journal
- J Med Chem
- Publish Year
- 2017
- Experiment Subject
- Experiment Type
- Others
- Phenotype Related
- Cancer
- Paper Title Cn
- Paper Title En
- Design, Synthesis, and Biological Activities of Vibsanin B Derivatives: A New Class of HSP90 C-Terminal Inhibitors
- Bilingual Status
- semi_complete