Ailanthone, natural compound isolated from Ailanthus altissima (Simaroubaceae), is a potent inhibitor of androgen receptor (AR) that blocks activities of full-length AR and AR splice variants. It overcomes MDV3100 (Enzalutamide)-resistance in castration-resistant prostate cancer cell lines. Ailanthone disrupts the interaction between AR and the chaperones HSP90, HSP70, and HSP40, which leads to AR ubiquitination and degradation.