Participation of MDM2 in Pro-Apoptotic and Androgen Receptor-Degrading Potency of Selected Steroid and Terpenoid Derivatives

This review aims to highlight anti-proliferative, pro-apoptotic, and androgen receptor-degrading activity of selected steroid and terpenoid derivatives in cancer cells, primarily in prostate cancer cells. Steroid and terpenoid derivatives (steroid hybrids, comprising androstane or pregnane skeleton associated with nitrogen containing heterocycle, some natural sterols, bile acids, and related semi-synthetic derivatives; oleanane and ursane type pentacyclic triterpenoids; lanostane and dammarane type tetracyclic triterpenoids), were reported earlier to cause the death of cancer cells via apoptosis; some compounds exhibited significant anticancer potency in vivo and may be considered as promising anticancer agents. The presented data indicate that direct interaction of steroid and terpenoid derivatives with the key oncogenic protein MDM2 makes a significant contribution to anti-proliferative, pro-apoptotic, and androgen receptor-degrading activity of these compounds. It triggers apoptosis, which leads to cell death. Structural optimization of steroid and terpenoid derivatives can significantly increase their affinity to MDM2 and improve their anti-proliferative, pro-apoptotic, and androgen receptor-degrading activity. © 2025 Elsevier B.V., All rights reserved.