Discovery and Optimization of Small Molecule Drug Leads and Probes
On March 5, the University of Houston Drug Discovery Institute hosted John Buolamwini, Ph.D. for a research talk entitled: “Discovery and Optimization of Small Molecule Drug Leads and Probes.”
Buolamwini's multidisciplinary approach integrates synthetic medicinal chemistry, computational modeling, and experimental techniques to target a variety of chronic diseases, including ischemic heart disease, cancer, HIV/AIDS and Alzheimer’s.
Buolamwini’s talk opened with a discussion of human concentrative nucleoside transporters (hCNTs) and the necessity of understanding their structure. Buolamwini explained how homology models for hCNT1, hCNT2, and hCNT3 were constructed using the crystal structure of a similar transporter in Vibrio cholerae bacteria as a template. Validation of these models was conducted through docking experiments with known inhibitors, revealing promising correlations, particularly for hCNT1. Subsequent virtual screening using the hCNT1 model identified 14 new inhibitors, showing the potential of these methods in drug discovery targeting nucleoside transporters.
Buolamwini also discussed another area of his research which focuses on targeting the constantly active STAT3 pathway in Glioblastoma (GBM), a tumor affecting the brain or spine. Buolamwini introduced SS-4, a novel small molecule designed to disrupt the STAT3-SH2 domain interaction. Computational modeling demonstrated SS-4's efficacy in blocking the activation of the STAT3 protein at low concentrations. In vitro studies confirmed SS-4's ability to suppress GBM cell proliferation and induce apoptosis (i.e., cell death), and in vivo experiments highlighted the potential of SS-4 as a therapeutic agent for GBM treatment.
Throughout the talk, Buolamwini emphasized the importance of interdisciplinary collaboration in addressing complex medical challenges. His innovations in drug design and discovery offer a promising outlook for improved patient outcomes through the development of novel therapeutics.
John Buolamwini, Ph.D. is chair of Pharmaceutical Sciences at Rosalind Franklin University. He has held faculty positions in the United States for the past 30 years, including the University of Mississippi and the University of Tennessee, where he served as the Vice Chair and Director of Graduate Programs of the Department of Pharmaceutical Sciences from 2012-2014.