PRMT5 IN-1 drochloride (compound 9), a hemiaminal, is a potent, selective protein arginine metltransferase 5 (PRMT5) inhibitor with an IC50 of 11 nM for PRMT5/MEP50. PRMT5 IN-1 drochloride can be converted to aldedes and react with C449 to form covalent adducts under psiological conditions.
PRMT5 IN-1 (compound 9; 0-500 nM) drochlorideinhibits the PRMT5/MEP50 complex [Kinact/KI=1.2×105 M-1 min-1] very rapidly with a Kinact of 0.068 min-1 and a good binding affinity (KI=55 nM)[1].PRMT5 IN-1 (0-1000 nM; 3 d; Granta-519 cells) drochloride inhibits the expression of cellular sDMA with an IC50 value of 0.012 μM[1].PRMT5 IN-1 (0-1 μM; 10 d; Granta-519 cells) drochloride inhibits cell proliferation in a dose-dependent manner with an IC50 value of 0.06 μM[1].
References:
[1]. Lin H, et, al. Discovery of Potent and Selective Covalent Protein Arginine Metltransferase 5 (PRMT5) Inhibitors. ACS Med Chem Lett. 2019 May 22;10(7):1033-1038.