Ailanthone

Ailanthone is an effective inhibitor of both full-length androgen receptor (AR) (IC50: 69 nM) and constitutively active truncated AR splice variants (IC50: 309 nM).Ailanthone 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 tumors. In addition, Ailanthone blocks tumor growth and metastasis of CRPC. Ailanthone has been shown to possess a growth-inhibitory effect against several cancer cell lines including R-HepG2, Jurkat, HeLa, HepG2, Hep3B, MCF-7, MDA-MB-231, and A549 cells. Ailanthone inhibits Huh7 cell growth through the induction of mitochondrion-mediated cell apoptosis and G0/G1 cell cycle arrest. Ailanthone-induced apoptosis is mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells.Ailanthone (i.p. or p.o.) has excellent efficiency for blocking the growth of CRPC xenografts. In pharmacokinetic studies, Ailanthone exhibits good solubility in water and good bioavailability (>20%). In addition, Ailanthone effectively suppresses CRPC tumor growth, despite not reaching a steady state of plasma drug concentration during the course of treatment.