A selective NVL inhibitor suppresses tumor growth by targeting ribosome biogenesis.

A selective NVL inhibitor, MM927, suppresses tumor growth in vivo by disrupting ribosome biogenesis without toxicity.

• Why it matters: Ribosome biogenesis is highly upregulated in cancer and essential for malignant growth, but pharmacological targeting has been unsuccessful, creating a need for new therapeutic strategies.
• What they did: Researchers identified NVL as a druggable target in ribosome assembly, discovered MM17 as an NVL inhibitor through forward genetics, and developed MM927, a more potent analog, to test in vivo effects.
• The result: MM927 inhibits NVL, disrupts 60S ribosomal subunit biogenesis, activates p53 without DNA damage, and suppresses tumor growth in vivo, establishing NVL inhibitors as promising cancer therapeutics.