AR and cancer: However, interpretation of the cellular activity of the SARM-nutlin PROTAC is complicated as AR is known to be a direct substrate of MDM2 [40], and nutlin itself induces ubiquitination and degradation of AR in cancer cells [41], raising the possibility of a direct modulatory effect of the SARM-nutlin bifunctional molecule on AR degradation independent of ternary complex formation [31,70].