M 1121 is a covalent and orally active inhibitor of the menin-MLL interaction capable of achieving complete and persistent tumor regression.

M-1121 (0~100 nM; 24 hours; MV4;11 cells) induces a dose-dependent decrease in HOXA9 and MEIS1 gene expression within the MLL-rearranged MV4;11 leukemia cell line, covalently bonds with Cysteine 329 in the menin MLL binding pocket, and significantly inhibits the proliferation of acute leukemia cell lines carrying MLL translocations, with no efficacy against native MLL cell lines, as revealed by RT-PCR analysis [1].

M-1121 administered orally at dosages of 100 mg/kg and 300 mg/kg over 26 days significantly impacts tumor volumes in SCID mice. The 100 mg/kg dosage reduces the average tumor volume by 32%, from 157 mm^3 to 106 mm^3 by day 26. Remarkably, the 300 mg/kg dosage achieves complete tumor regression in all treated mice (10/10), with no tumor regrowth observed up to one month post-treatment. Additionally, at a lower dosage of 5 mg/kg in female C57BL/6 mice, M-1121 exhibits a low clearance and a moderate volume of distribution. These findings underscore M-1121's potent antitumor efficacy and favorable pharmacokinetic profile[1].