Enzomenib

Enzomenib is an inhibitor of the protein-protein interaction between menin and mixed-lineage leukemia 1 (MLL1). It binds to menin (Kd = 6 nM) and inhibits the menin-MLL1 interaction with an IC50 value of 1. nM. Enzomenib selectively inhibits the growth of MV4-11, MOLM-13, KOPN-8, and OCI-AML-3 leukemia cells (IC50s = 10, 15, 31, and 15 nM, respectively), which contain MLL rearrangement (MLL-r) or NPM1 mutations, over HL-60, MOLT-4, and Reh leukemia cells (IC50s = >10 µM for all), which do not have MLL-r or NPM1 mutations. In vivo, enzomenib (25 and 50 mg/kg) has antitumor activity in a mouse xenograft model using MV4-11 cells, which express an MLL-AF4 gene fusion. InChI: InChI=1S/C33H43FN6O3/c1-20(2)40(21(3)4)31(41)26-15-23(34)6-9-27(26)43-28-16-35-19-36-30(28)39-17-33(18-39)10-12-38(13-11-33)32(42)29-25-8-7-24(37-29)14-22(25)5/h6,9,15-16,19-21,24-25,29,37H,5,7-8,10-14,17-18H2,1-4H3/t24-,25+,29-/m0/s1, InChIKey: JQHJEDMMWUIYCE-FVVBACEJSA-N, SMILES: O=C([C@@H]1[C@@]2([H])C(C[C@@](CC2)([H])N1)=C)N3CCC4(CC3)CN(C4)C5=NC=NC=C5OC6=C(C(N(C(C)C)C(C)C)=O)C=C(F)C=C6