Arg-PEG1-Tαsyn

Arg-PEG1-Tαsyn is a PROTAC degrader targeting α-synuclein (α-syn), with a DC50 of 0.28 μM in U251 cells. This compound utilizes arginine (Arg) as the E3 ligase ligand and a benzothiazole-aniline variant as the warhead for α-syn targeting. It effectively degrades both wild-type α-syn and its A53T mutant in mammalian cells. In vitro, Arg-PEG1-Tαsyn significantly reduces α-syn aggregation via the E3 ubiquitin ligase UBR1. In vivo, it demonstrates good safety and significantly improves dopaminergic neuron damage and motor dysfunction. Arg-PEG1-Tαsyn is useful in Parkinson's disease research.