Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia.

doi:10.1172/JCI129126

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Article

Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia.

The Journal of clinical investigation - 3 Feb 2020

Klossowski Szymon, Miao Hongzhi, Kempinska Katarzyna, Wu Tao, Purohit Trupta, Kim EunGi, Linhares Brian M, Chen Dong, Jih Gloria, Perkey Eric, Huang Huang, He Miao, Wen Bo, Wang Yi, Yu Ke, Lee Stanley Chun-Wei, Danet-Desnoyers Gwenn, Trotman Winifred, Kandarpa Malathi, Cotton Anitria, Abdel-Wahab Omar, Lei Hongwei, Dou Yali, Guzman Monica, Peterson Luke, Gruber Tanja, Choi Sarah, Sun Duxin, Ren Pingda, Li Lian-Sheng, Liu Yi, Burrows Francis, Maillard Ivan, Cierpicki Tomasz, Grembecka Jolanta

Abstract excerpt

The protein-protein interaction between menin and mixed lineage leukemia 1 (MLL1) plays a critical role in acute leukemias with translocations of the MLL1 gene or with mutations in the nucleophosmin 1 (NPM1) gene. As a step toward clinical translation of menin-MLL1 inhibitors, we report development of MI-3454, a highly potent and orally bioavailable inhibitor of the menin-MLL1 interaction. MI-3454 profoundly...

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PMID: 31855575
DOI: 10.1172/JCI129126
PMCID: PMC6994154

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