Synonyms: compound 151 [US10781218B2] | KO-539 | KO539
Compound class:
Synthetic organic
Comment: We obtained the chemical structure for ziftomenib from WHO Proposed list 125 of July 2021. This mapped to PubChem CID 138497449, and to the small molecule KO-539 (Kura Oncology). KO-539 is an orally bioavailable, clinical stage agent that was designed to disrupt the protein-protein interaction between tumour suppressor menin (MEN1, O00255) and MLL oncoproteins (re-arranged lysine (K)-specific methyltransferases) as a mechanism to treat acute myeloid leukemia (AML) [1,3]. The menin-MLL interaction is an essential upregulator of the expression of genes such as HOXA9 and MEIS1 that are involved in the development of AML. Blocking the menin-MLL interaction is predicted to induce terminal differentiation of AML blasts by reducing transcription of the HOXA9 and MEIS1 AML promoters. KO-539 binds to menin [2].
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References |
1. Fiskus W, Daver N, Boettcher S, Mill CP, Sasaki K, Birdwell CE, Davis JA, Das K, Takahashi K, Kadia TM et al.. (2022)
Activity of menin inhibitor ziftomenib (KO-539) as monotherapy or in combinations against AML cells with MLL1 rearrangement or mutant NPM1. Leukemia, 36 (11): 2729-2733. [PMID:36151141] |
2. Wu T, Li L, Wang Y, Ren P, Grembecka J, Cierpicki T, Klossowski S, Pollock J, Borkin D. (2020)
Substituted inhibitors of menin-MLL and methods of use. Patent number: US10781218B2. Assignee: University of Michigan, Kura Oncology Inc. Priority date: 16/03/2016. Publication date: 22/09/2020. |
3. (2021)
AML Prognoses Better with Menin-MLL Inhibitor?. Cancer Discov, 11 (2): 216-217. [PMID:33380450] |