NVL inhibitor MM927 is a bioavailable analog of MM17 and potent inhibitor of 60S ribosomal subunit assembly factor NVL with IC50 of 51 nM in cells expressing ectopic human NVL, inhibits HCT116 growth in a dose-dependent manner with IC50 of 53 nM.
MM927 also inhibits mouse NVL with an IC50 of 0.207 µM。
MM927 is a structurally related compound with improved metabolic stability compared with MM17.
MM927 reduces viability through the same mechanism as MM17, by blocking 60S biogenesis via NVL inhibition.
MM927 induces half-mer polysomes in polysome profiles and arrests 60S ribosome biogenesis in the nucleolus.
MM927 also triggers cell cycle arrest at both the G1/S and G2/M transitions, mirroring the effects of MM17, with G1/S arrest partially and G2/M arrest fully dependent on p53.
MM927 (35 mg/kg, i.p.) inhibits colorectal and leukemia tumor xenograft growth in vivo without overt toxicity.
MM927 inhibit ribosome biogenesis without causing DNA damage.