New study below.
The Tree of Heaven is an invasive species. It spreads via suckers & has a very effective way of dealing with competition: it produces Ailanthone, a very effective herbicide.
Ailanthone is also used as an antimalarial drug.
Ailanthone "possesses favourable drug-like properties such as good bioavailability, high solubility, lack of CYP inhibition and low hepatotoxicity."
The heat shock protein [HSP] family is frequently brought into play by advanced PCa. Heat treatment is only one of the triggers for HSP presence. One of the protections that HSP offers PCa is a chaperone protein that escorts the androgen receptor [AR] on its journey to the nucleus.
In the current study, Ailanthone "binds to the co-chaperone protein p23 and prevents AR's interaction with HSP90". This is followed by "degradation of AR".
"Ailanthone ... as a potent inhibitor of both full-length AR ... and constitutively active truncated AR splice variants (AR-Vs)." i.e., such as AR-V7.
Ailanthone "blocks tumour growth and metastasis of CRPC."
Step 1: Togo seems to be the best bet for contracting malaria. LOL
Nat Commun. 2016 Dec 13;7:13122. doi: 10.1038/ncomms13122.
Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer.
He Y1, Peng S1, Wang J1, Chen H1, Cong X1, Chen A1, Hu M1, Qin M1, Wu H1, Gao S1, Wang L2, Wang X1, Yi Z1, Liu M1,3.
1East China Normal University and Shanghai Fengxian District Central Hospital Joint Center for Translational Medicine, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
2Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
3Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Houston, Texas 77030, USA.
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.
PMID: 27959342 DOI: 10.1038/ncomms13122
[PubMed - in process]