MM927

MM927 is a potent, orally bioavailable small molecule inhibitor of nuclear valosin-containing protein-like (NVL), a hexameric AAA+ ATPase essential for the assembly of the large ribosomal subunit (60S). Developed as an optimized analog of the dibenzothiazepinone MM17, MM927 blocks ribosome biogenesis, a process frequently upregulated in cancer cells to support rapid proliferation. Inhibition of NVL by MM927 disrupts 60S assembly and leads to the stabilization of p53 via MDM2, resulting in cell cycle arrest or apoptosis without inducing DNA damage. In preclinical studies, MM927 has demonstrated efficacy in suppressing tumor growth in mouse models of colorectal cancer, validating NVL as a therapeutic vulnerability.