RapaGlues and RapaTags - A Bridge between Macrocyclic Peptides and Molecular Glues for Interrogating Hard to Drug Targets
Rick Ewing
VP, Head of Chemistry, Rapafusyn
Non-degrading molecular glues are of high interest to drug discovery programs. The natural products rapamycin, FK506, cyclosporin and related analogs have delivered several marketed drugs. Despite these successes, there remain few approaches towards finding novel chemical matter in this area. Rapafusyns platform are macrocyclic peptidic molecular glues (RapaGlues) that concomitantly bind FKBP12 and a disease target to form a ternary complex. These compounds can be made via modular synthesis in both DEL and array library format to screen against a broad range of difficult to drug intracellular and transmembrane targets. RapaGlues have been screened against a number of hard to drug targets. The presentation will describe the identification of peptidic molecular glues and discuss SAR related to cell permeability and druggability.