Onametostat (JNJ-64619178) is a selective, orally active and pseudo-irreversible protein arginine methyltransferase 5 (PRMT5) inhibitor with an IC50 of 0.14 nM. Onametostat has potent activity in lung cancer[2].IC50 & Target:IC50: 0.14 nM (PRMT5)[2]In Vitro:Onametostat binds simultaneously to the S-adenosylmethionine (SAM)- and protein substrate- binding pockets of the PRMT5/MEP50 complex with a pseudo-irreversible mode-of-action. Onametostat shows potent and broad inhibition of cellular growth.In Vivo:Oral administration of Onametostat results in efficient inhibition of dimethylation of SMD1/3 proteins, components of the splicing machinery and direct substrates of the methylosome, in several non-small cell lung cancer and small cell lung cancer cancer mouse xenograft models.