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PROTAC (MetRS-pomalidomide)
- Development stage
- Preclinical
- Lead developer
- University of Washington
- Modality
- PROTACs (E3 ligase recruitment) → Targeted Protein Degraders (TPDs) → Small Molecules, Bivalent/Multivalent Binders → Multivalent & Scaffold-Based Small Molecules → Small Molecules
01
Overview
PROTAC (MetRS-pomalidomide) is a preclinical-stage proteolysis-targeting chimera (PROTAC) designed for the treatment of Trypanosoma cruzi infections (Chagas disease) [1]. Developed by researchers at the University of Washington, this heterobifunctional small molecule consists of MRS2718, a selective ligand targeting T. cruzi methionyl-tRNA synthetase (MetRS), conjugated via a linker to pomalidomide, which engages the host E3 ubiquitin ligase cereblon (CRBN) [1]. By simultaneously binding MetRS and cereblon, the PROTAC induces the ubiquitination and subsequent proteasomal degradation of MetRS, leading to potent inhibition of T. cruzi growth in mammalian host cells [1].
- Other names
- MetRS-pomalidomide PROTACPROTAC linking pomalidomide and MRS2718
02
Targets
CRBN (Cereblon)MetRS (Methionyl-tRNA synthetase)
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