Androgen receptor (AR) plays the key role in the early-or late-prostate cancer.The cancer progression is correlated to AR transactivation which is mediated by several AR coregulaors such as ARA70, ARA54, and ARA55.Here we develop a curcumin derivative compound to selectively degrade AR via interruption ofAR-AR coactivators interaction in selective prostate cells that lead to suppress AR-induced prostate cancer growth.Mechanistic dissection showed this compound promotes AR degradation via proteasome degradation pathway to enhance the ARoMdm2 complex to let AR to be more vulnerable to be degraded by proteases.