CHEN RESEARCH GROUP
上善若水
厚德载物
Zampanolide Mimics as Anti-Prostate Cancer Agents
The marine macrolide (-)-zampanolide is a unique microtubule-stabilizing agent with covalent-binding with tubulin and superior cytotoxic potency compared to paclitaxel against multi-drug resistant cancer cell lines. However, the limited availability of zampanolide from both isolation and synthetic efforts constitutes a serious obstacle to support further drug development activities. More importantly, we envision that zampanolide possesses poor pharmacokinetic profiles as a drug candidate due to it chemically fragile side chain and metabolically vulnerable lactone moiety. We have been working to develop stabilized and simplified zampanolide mimics to improve their pharmacokinetic profiles, therapeutic window, and synthetic efficiency yet retain the impressive therapeutic potency for potentially clinical treatment of castration-resistant prostate cancer.
Development of new androgen receptor antagonists for castration-resistant prostate cancer
Prostate cancer is still a major public health problem that affects men worldwide and continues to be the second leading cause of cancer death in American men. Over 33,000 men die each year of castration-resistant prostate cancer due to the inevitable progression of resistance to the current treatments. Castration-resistant prostate cancer is still driven by the androgen receptor-regulated gene expression. The proposed research aims to develop new androgen receptor antagonists with different chemical scaffolds from current available treatments for the clinical treatment of castration-resistant prostate cancer.
Fighting Prostate Cancer with AR-PROTACs
Androgen receptor PROTACs (Proteolysis Targeting Chimeras) have been verified in cell culture and animal models to be a better therapeutic modality than androgen receptor antagonists due to the event-driven mechanism. This project aims to discover efficient androgen receptor-based PROTACs to combat the deadly castration-resistant prostate cancer.
