A suite of mathematical solutions to describe ternary complex formation and their application to targeted protein degradation by heterobifunctional ligands.

ABSTRACT: Small molecule-induced targeted protein degradation by heterobifunctional ligands or molecular glues represents a new modality in drug development, allowing development of therapeutic agents for targets previously considered undruggable. Successful target engagement requires the formation of a ternary complex (TC) when the ligand brings its target protein in contact with an E3 ubiquitin ligase. Unlike traditional drugs, where target engagement can be described by a simple bimolecular equilibrium equation, similar mathematical tools are currently not available to describe TC formation in a universal manner. This current limitation substantially increases the challenges of developing drugs with targeted protein degradation mechanism. In this article, I provide a full, exact, and universal ma

SUBMITTER: Han B 

PROVIDER: S-EPMC7650257 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature