Type I PRMT inhibitors

Type I PRMT inhibitors are a class of small-molecule therapeutics being developed by the Amyotrophic Lateral Sclerosis Therapy Development Institute (ALS TDI) for the treatment of C9orf72-related Amyotrophic Lateral Sclerosis (ALS). The program focuses on inhibiting Type I protein arginine methyltransferases (PRMTs) to block the asymmetric dimethylation of arginine-rich dipeptide repeat proteins (DPRs), specifically polyGR and polyPR. These toxic DPRs are produced via non-canonical translation of the hexanucleotide repeat expansion in the C9orf72 gene, a common genetic cause of ALS. Preclinical research suggests that reducing the asymmetric dimethylation of these proteins mitigates their neurotoxicity. The program is currently in the preclinical stage, with various tool compounds like MS023 and GSK3368715 having been used to validate the target.

Other names

asymmetric dimethylation inhibitorsType I protein arginine methyltransferase inhibitors