The Department of Pharmaceutical Sciencies invites you to attend a seminar on Monday, October 8, 2018, 3:30 - 4:30pm, Pharmacy/Biology Building (PBB) room 129
Paul M. Scola, Ph.D.
Director of Chemistry in Drug Discovery Research, Bristol-Myers Squibb
Seminar Title: “Discovery of a Macrocyclic Peptide Inhibitor(BMS-986189) of Programmed Death-Ligand 1 (PD-L1)”
Macrocyclic peptides were identified as inhibitors of PD-L1 through mRNA display, an in vitro selection technique. These screening leads demonstrated modest in vitro activity in PD-L1 binding assays, while they proved inactive in functional assays. Co-crystal structures of selected analogues with PD-L1 provided insight into the nonbonding interactions between these macrocyclic peptides and the PD-L1 protein. The structure-based insights gleaned enabled the rapid optimization of these macrocycles with respect to PD-L1 inhibitory activity and the mitigation of off-target liabilities identified in early leads. This rational drug design approach led to the discovery of a macrocyclic peptide (BMS-986189) with activity in binding and functional assays comparable to a PD-L1 antibody. Details of these discoveries will be discussed.
Monday, October 8, 2018; 3:30-4:30pm
Pharmacy/Biology Building (PBB) room 129
Host: Dr. M. Kyle Hadden 860-486-8446
kyle.hadden@uconn.edu
For more information, contact: Kyle Hadden at 860.486.8446