Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity

The goal of this study is to evaluate the pharmocological novel inhibitor of PRMT5 namely JNJ-64619178 on clones derived from K562 cell lines which have been CRISPR engineered to carry mutations frequently observed in hematologic cancers on splicing factor SF3B1. Overall design: SF3B1 specific guide RNAs which harbored specific mutations were used to target the nucleotides that code for Lysine at amino acid positions 700 (K700) to be converted to Glutamic acid(E) so as to obtain K700E alleles in K562 cell lines . Subsequently, RNA-sequencing was carried out from individual clones.