AMG-193 is an orally active and MTA-cooperative inhibitor of PRMT5 with potent biochemical and cellular activity. AMG-193, in combination with MTA, selectively targets and inhibits the growth of MTAP-deficient tumor cells by suppressing PRMT5, with an IC50 of 0.107 μM, while sparing normal cells that possess wild-type MTAP. AMG-193 also exhibits antitumor activity.