Ziftomenib

Cell lines

Acute myeloid leukemia (AML) cells (OCI-AML3, MOLM13 and MV411 cells)

Preparation Method

OCI-AML3, MOLM13 and MV411 cells were incubated with 150nM Ziftomenib for 3-4 days, followed by RNA sequencing.

Reaction Conditions

150nM; 3-4 days

Applications

Ziftomenib uniformly induced transcriptional downregulation of MEIS1, PBX3, FLT3, and BCL2 in all NPM1^mut (OCI-AML3 cells) and MLL-r cells (MOLM13 and MV411 cells) and demonstrated high consistency with the effects of other menin inhibitors.

Animal models

NSG mice

Preparation Method

NSG mice were engrafted with luciferized patient-derived MLL-AF9+FLT3-TKD expressing Acute myeloid leukemia (AML) cells and monitored for 5-7 days. Mice were imaged by Xenogen camera, randomized to equivalent bioluminescence and treated with vehicle, 75mg/kg of Ziftomenib (p.o., daily×5 days) and/or 30mg/kg of OTX015 (p.o., daily×5 days), or 30mg/kg of venetoclax (p.o., daily×5 days) for 2 weeks. Total bioluminescent flux was determined for each cohort by Xenogen camera.

Dosage form

75mg/kg; 5 days; p.o.

Applications

Whereas monotherapy with relatively low dose of venetoclax or OTX015 alone for 2 weeks Exhibited modest reduction of AML burden, treatment with Ziftomenib alone induced marked and significant reduction in AML burden.

References:
[1]Rausch J, Dzama M M, Dolgikh N, et al. Menin inhibitor ziftomenib (KO-539) synergizes with drugs targeting chromatin regulation or apoptosis and sensitizes acute myeloid leukemia with MLL rearrangement or NPM1 mutation to venetoclax[J]. Haematologica, 2023, 108(10): 2837.
[2]Fiskus W, Daver N, Boettcher S, et al. Activity of menin inhibitor ziftomenib (KO-539) as monotherapy or in combinations against AML cells with MLL1 rearrangement or mutant NPM1[J]. Leukemia, 2022, 36(11): 2729-2733.