117977-20-5Relevant articles and documents
Proton pump inhibitors selectively suppress MLL rearranged leukemia cells via disrupting MLL1-WDR5 protein-protein interaction
Chen, Wei-Lin,Chen, Xin,Guo, Xiao-Ke,Jiang, Zheng-Yu,Li, Dong-Dong,Wang, Ying-Zhe,Xu, Jun-Jie,You, Qi-Dong
, (2020)
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 in-house 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.
PROCESS FOR THE PREPARATION OF RABEPRAZOLE
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Page/Page column 14, (2014/07/07)
The present invention provides a compound of Formula III, process of its preparation and its use as a reference marker or as a reference standard. The present invention further provides a process for the preparation of rabeprazole, a salt or a solvate thereof. The invention also provides a chromatographic method for testing the purity of rabeprazole, a salt or a solvate thereof.
SALTS OF BENZIMIDAZOLE DERIVATIVE WITH AMINES AND PROCESS FOR PRODUCTION THEREOF
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Page/Page column 13, (2008/06/13)
It is an object of the present invention to provide (1) a process for manufacturing alkali metal salts of 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylsulfinyl]-1 H -benzimidazole which are useful as gastric acid secretion inhibitors, anti-ulcer agents and other drugs and (2) salts of 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylsulfinyl]-1 H -benzimidazole with amines which are intermediates for the production of the alkali metal salts, and a process for manufacturing the same. According to the present invention, disclosed are salts represented by the following formula (I): (wherein A + represents an isopropylammonium ion, sec-butylammonium ion or cyclopentylammonium ion).
