MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with <i>MTAP</i> -Deleted Cancer

Abstract

PRMT5 was identified as a synthetic lethal target for MTAP del cancers; however, previous PRMT5 inhibitors do not selectively target this genotype. The differentiated binding mode of MRTX1719 leverages the elevated MTA in MTAP del cancers and represents a promising therapy for the ∼10% of patients with cancer with this biomarker. See related commentary by Mulvaney, p. 2310. This article is featured in Selected Articles from This Issue, p. 2293.