Medicinal Chemistry Graduate Student Seminar Series: Cole Stephens

U-M College of Pharmacy Medicinal Chemistry Graduate Student Seminar Series: Cole Stephens

Department: Medicinal Chemistry

Speaker: Cole Stephens, Third Year Graduate Student, Department of Medicinal Chemistry, College of Pharmacy, University of Michigan

Title: Advances Towards the Development of Small Molecule Pregnancy Associated Plasma Protein A Inhibitors

Abstract: Key to the successful development of any drug or therapeutic is the identification and validation of a suitable biomolecular target which can be safely and effectively modulated to elicit a clinically relevant effect. Pregnancy associated plasma protein A (PAPP-A) is one such potential target which has gained increasing attention for the treatment of a variety of diseases. Despite this attention, methods to study PAPP-A’s role in physiology and disease remain largely constrained to knock-out and knock-down studies with limited throughput and transferability. To address this bottleneck, novel chemical tools are needed to enable the probing of PAPP-A function in a variety of biological contexts. This talk will focus on the avenues we are pursuing for the discovery and design of novel small molecule PAPP-A inhibitors. It will encompass a cheminformatics driven high-throughput screening workflow for the identification of novel inhibitor scaffolds, followed by their biochemical and functional characterization. In parallel, we are studying the endogenous PAPP-A inhibitor stannioclacin 1 (STC1) and will discuss the biophysical and structural characterization of this complex. Finally, the future directions of this work will be highlighted to help guide the study of PAPP-A as a therapeutic target.