Arg-PEG1-Talphasyn is a PROTAC degrader targeting alpha-synuclein (alpha-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 alpha-syn targeting. It effectively degrades both wild-type alpha-syn and its A53T mutant in mammalian cells. In vitro, Arg-PEG1-Talphasyn significantly reduces alpha-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-Talphasyn is useful in Parkinsons disease research.
Target:
PROTACs
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