SNDX-5613

SNDX-5613 is a derivative of VTP-50469 (Item No. 40759), an inhibitor of the protein-protein interaction between menin and mixed-lineage leukemia 1 (MLL1), also known as lysine methyltransferase 2A (KMT2A). It inhibits the growth of patient-derived acute myeloid leukemia (AML) cells expressing the gene encoding upstream binding factor (UBF) and containing tandem duplications (UBF-TDs) when UBF-TD-containing AML cells are co-cultured with mesenchymal stem cells.¹ SNDX-5613 (50 mg/kg) reduces disease burden and improves survival when used alone and, to a greater extent, when used in combination with the CBP and p300 inhibitor GNE-781 (Item No. 36450) in a MOLM-13 mouse xenograft model.² It also reduces disease burden and increases survival in patient-derived xenograft (PDX) mouse models in which tumor cells contain rearrangements in the gene encoding KMT2A or mutations in the gene encoding nucleophosmin 1 (NPM1).³

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1. Barajas, J.M., Rasouli, M., Umeda, M., et al. Acute myeloid leukemias with UBTF tandem duplications are sensitive to menin inhibitors. Blood 143(7), 619-630 (2024).

2. Fiskus, W., Mill, C.P., Birdwell, C., et al. Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1. Blood Cancer J. 13(1), 53 (2023).

3. Issa, G.C., Aldoss, I., Dipersio, J., et al. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature 615(7954), 920-924 (2023).