Proton pump inhibitors selectively suppress MLL rearranged leukemia cells via disrupting MLL1-WDR5 protein-protein interaction was written by Chen, Wei-Lin;Li, Dong-Dong;Chen, Xin;Wang, Ying-Zhe;Xu, Jun-Jie;Jiang, Zheng-Yu;You, Qi-Dong;Guo, Xiao-Ke. And the article was included in European Journal of Medicinal Chemistry in 2020.Application of 117976-90-6 The following contents are mentioned in the article:
Genetic rearrangements of the mixed lineage leukemia (MLL) leading to oncogenic MLL-fusion proteins (MLL-FPs). MLL-FPs occur in about 10% of acute leukemias and are associated with dismal prognosis and treatment outcomes which emphasized the need for new therapeutic strategies. In present study, by a cell-based screening inhouse compound collection, we disclosed that Rabeprazole specially inhibited the proliferation of leukemia cells harboring MLL-FPs with little toxicity to non-MLL cells. Mechanism study showed Rabeprazole down-regulated the transcription of MLL-FPs related Hox and Meis1 genes and effectively inhibited MLL1 H3K4 methyltransferase (HMT) activity in MV4-11 cells bearing MLL-AF4 fusion protein. Displacement of MLL1 probe from WDR5 protein suggested that Rabeprazole may inhibit MLL1 HMT activity through disturbing MLL1-WDR5 protein-protein interaction. Moreover, other proton pump inhibitors (PPIs) also indicated the inhibition activity of MLL1-WDR5. Preliminary SARs showed the structural characteristics of PPIs were also essential for the activities of MLL1-WDR5 inhibition. Our results indicated the drug reposition of PPIs for MLL-rearranged leukemias and provided new insight for further optimization of targeting MLL1 methyltransferase activity, the MLL1-WDR5 interaction or WDR5. This study involved multiple reactions and reactants, such as Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6Application of 117976-90-6).
Sodium 2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)benzo[d]imidazol-1-ide (cas: 117976-90-6) belongs to imidazole derivatives. Imidazole derivatives generally have good solubility in protic solvents. Simple imidazole derivatives, such as 1H-imidazole, 2-methyl-1H-imidazole, and 1,2-dimethylimidazole, have very high solubility in water. This ring system is present in important biological building blocks, such as histidine and the related hormone histamine.Application of 117976-90-6
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem