ReferenceID 504
Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer
Nat Commun
Androgen receptor (AR) antagonist MDV3100 is the first therapeutic approach in treating castration-resistant prostate cancer (CRPC), but tumours frequently become drug resistant via multiple mechanisms including AR ampli
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 504
- Evidence Id
- 17094
- Core Evidence Id
- 17094
- Source Reference Id
- 981
- Herb2 Reference Id
- HBREF001692
- Subject Paper Key
- HBIN014942_27959342
- Pubmed Id
- 27959342
- Doi
- 10.1038/ncomms13122
- Paper Title
- Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer
- Paper Abstract
- Androgen receptor (AR) antagonist MDV3100 is the first therapeutic approach in treating castration-resistant prostate cancer (CRPC), but tumours frequently become drug resistant via multiple mechanisms including AR amplification and mutation. Here we identify the small molecule Ailanthone (AIL) as a potent inhibitor of both full-length AR (AR-FL) and constitutively active truncated AR splice variants (AR-Vs). AIL binds to the co-chaperone protein p23 and prevents AR's interaction with HSP90, thus resulting in the disruption of the AR-chaperone complex followed by ubiquitin/proteasome-mediated degradation of AR as well as other p23 clients including AKT and Cdk4, and downregulates AR and its target genes in PCa cell lines and orthotopic animal tumours. In addition, AIL blocks tumour growth and metastasis of CRPC. Finally, AIL possesses favourable drug-like properties such as good bioavailability, high solubility, lack of CYP inhibition and low hepatotoxicity. In general, AIL is a potential candidate for the treatment of CRPC.
- Journal
- Nat Commun
- Publish Year
- 2016
- Experiment Subject
- pca cell lines
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer
- Bilingual Status
- semi_complete