In Silico Design, Synthesis, and Evaluation of PROTAC Against Hematopoietic Prostaglandin D Synthase.

ABSTRACT

Chemical protein knockdown technology using proteolysis-targeting chimeras (PROTACs) to hijack the endogenous ubiquitin-proteasome system is a powerful strategy to degrade disease-related proteins. This chapter describes in silico design of a hematopoietic prostaglandin D synthase (H-PGDS) degrader, PROTAC(H-PGDS), using a docking simulation of the ternary complex of H-PGDS/PROTAC/E3 ligase as well as the synthesis of the designed PROTAC(H-PGDS)s and evaluation of their H-PGDS degradation activity.