RVU305

RVU305 is a small molecule, oral, brain-penetrant MTA-cooperative inhibitor of protein arginine methyltransferase 5 (PRMT5), developed by Ryvu Therapeutics. It is designed to selectively inhibit the growth of cancer cells with deletions in the MTAP gene (methylthioadenosine phosphorylase), which are present in approximately 10–15% of all human tumors. MTAP deletion leads to accumulation of methylthioadenosine (MTA) within cells; at high concentrations, MTA acts as a selective inhibitor of PRMT5 by competing with its substrate S-adenosylmethionine (SAM). In preclinical studies, RVU305 demonstrated robust antiproliferative activity and tumor growth inhibition in MTAP-null cancer models—including those resistant to immune checkpoint inhibitors—while sparing normal cells. The compound has shown CNS penetration and predicted therapeutic exposure in brain tissue. As of June 2025, it remains in preclinical/IND-enabling development for solid tumors characterized by MTAP deletion[1][2][3][4][5][6][7].