Menin-MLL inhibitor-22 (compound C20) is an orally active inhibitor of the interaction between menin and mixed lineage leukemia (MLL) (IC50=7 nM). Menin-MLL inhibitor-22 binds menin protein and inhibits cancer cell growth (MV4 cells, IC50=0.3 μM). Menin is a putative tumor suppressor associated with multiple endocrine neoplasia type 1 (MEN-1 syndrome).
Menin-MLL inhibitor-22 (1 μM; 60 min) possesses good stability and low clearance rate in liver microsomes[1].Menin-MLL inhibitor-22 (1 and 10 μM; 24 h) inhibits MLL-r Leukemia cells MV4;11 growth and (0.1-10 μM; 24 h) decreases the expression of the HOXA9 and MEIS1 induced by menin-MLL interaction[1]. Menin-MLL inhibitor-22 (1, and 10 μM; 7 d) increases the amount of CD11b, a differentiation marker of myeloid cells, indicating a reverse the differentiation arrest of MLL-r leukemia cells[1].Menin-MLL inhibitor-22 (1, and 10 μM; 24 h) induces cell apoptosis and G0/G1 cell cycle arrest[1].
Menin-MLL inhibitor-22 (6 mg/kg and 30 mg/kg; p.o.; every second day for 16 days) shows potent antitumor activity in the MV4;11 subcutaneous xenograft models of MLL-rearranged leukemia[1].Pharmacokinetic Properties in SD Rats[1]
References:
[1]. Lei H, et al. Discovery of Novel, Potent, and Selective Small-Molecule Menin-Mixed Lineage Leukemia Interaction Inhibitors through Attempting Introduction of drophilic Groups. J Med Chem. 2022 Oct 13;65(19):13413-13435.