Chemistry Final Defense – Ho Sog (Sogi) Yoon

About the event

Speaker:  Ho Sog (Sogi) Yoon

Group:  Dr. Cliff Berkman

Title: The Development of PSMA-Targeted Drug Conjugates

Abstract:

Prostate cancer ranks as the third most common cause of cancer-related deaths among American men. Historically, treatments for prostate cancer have faced challenges with off-target effects and a lack of specificity, leading to diminished treatment efficacy and potential impacts on the patients’ quality of life. Efforts in targeted therapy focus on the delivery of cytotoxic agents to diseased tissue to achieve a controlled therapeutic outcome. Prostate-specific membrane antigen (PSMA) being a dominant enzyme-biomarker associated with prostate cancer makes it an ideal target for various approaches, including antibodies, imaging agents, radiotherapeutics, and small-molecule drug conjugates (SMDC). Like many other groups in the field of targeted drug delivery, we have developed a phosphoramidate-based inhibitor which has a high-affinity for PSMA. This inhibitor binds irreversibly to PSMA and can deliver a diverse array of payloads to PSMA (+) cells. Current research in the Berkman lab focuses on the development of drug-delivery platforms that includes: (1) a cytotoxic agent, (2) a novel pH-sensitive linker, and (3) a small molecule targeting ligand for PSMA. Recent work in our group was the development of pH sensitive phosphoramidate scaffolds. Our goal was to design a modular drug-delivery platform for prostate cancer that allows for late-stage modifications without compromising its affinity for PSMA. The work detailed in this report demonstrates the selectivity and effectiveness of our PSMA-targeted SMDCs against PSMA (+) cell lines, exploration of self-immolative spacers to be incorporated into our phosphoramidate scaffolds, and the synthesis of a second-generation phosphoramidate-based SMDCs to broaden the application of clinically relevant targeted chemotherapeutic agents for prostate cancer therapy.