Introduction
Purinergic GPCRs, including receptors for adenosine and extracellular nucleotides, play critical roles in inflammatory signaling, neurological processes, and chronic pain biology. This session examines how structure-based approaches have guided the discovery of selective ligands targeting these receptors.
Drawing on decades of medicinal chemistry research, the course explores the development of A3 adenosine receptor agonists and P2Y14 receptor antagonists, integrating chemical synthesis, pharmacological characterization, and computational modeling. Participants will also examine emerging insights into extrahelical allosteric binding sites and their implications for GPCR modulation.
The session is designed for PhD scientists, postdoctoral researchers, and industry professionals interested in translational pharmacology and GPCR-targeted drug discovery.
Instructors
Kenneth A. Jacobson
Dr. Kenneth A. Jacobson is Chief of the Molecular Recognition Section in the Laboratory of Bioorganic Chemistry at the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.
A medicinal chemist specializing in the structure and pharmacology of G protein-coupled receptors and ion channels, his research focuses particularly on purinergic receptors for adenosine, ATP, and related nucleotides. He earned a B.A. from Reed College and a Ph.D. in Chemistry from the University of California, San Diego, followed by postdoctoral training at the Weizmann Institute of Science.
Dr. Jacobson’s contributions to receptor pharmacology and medicinal chemistry have been recognized with numerous honors including the Medicinal Chemistry Hall of Fame, the Smissman Award, and the Goodman and Gilman Award. His expertise underpins the strategies discussed in this Masterclass.
Matteo Pavan
Matteo Pavan, PhD, is a molecular modeler and visiting postdoctoral researcher in the Laboratory of Bioorganic Chemistry at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, working under the direction of Dr. Kenneth Jacobson.
His research focuses on developing computational pipelines for rational ligand design targeting therapeutically relevant receptors, with emphasis on GPCRs within the purinergic signaling family. His work integrates molecular dynamics, virtual screening, and early-stage lead optimization to support medicinal chemistry programs.
He received his PhD in Molecular Sciences from the University of Padua in 2023 under the supervision of Prof. Stefano Moro. In this Masterclass, he presents computational and SAR studies identifying an extrahelical allosteric site on the A3 adenosine receptor.
