In 2019,Journal of Medicinal Chemistry included an article by Liang, Xiaofei; Wang, Beilei; Chen, Cheng; Wang, Aoli; Hu, Chen; Zou, Fengming; Yu, Kailin; Liu, Qingwang; Li, Feng; Hu, Zhenquan; Lu, Tingting; Wang, Junjie; Wang, Li; Weisberg, Ellen L.; Li, Lili; Xia, Ruixiang; Wang, Wenchao; Ren, Tao; Ge, Jian; Liu, Jing; Liu, Qingsong. Related Products of 1193-21-1. The article was titled 《Discovery of N-(4-(6-acetamidopyrimidin-4-yloxy)phenyl)-2-(2-(trifluoromethyl)phenyl)acetamide (CHMFL-FLT3-335) as a potent FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutant selective inhibitor for acute myeloid leukemia》. The information in the text is summarized as follows:
Most of the current FMS-like tyrosine kinase 3 (FLT3) inhibitors lack selectivity between FLT3 kinase and cKIT kinase as well as the FLT3 wt and internal tandem duplication (ITD) mutants. We report a new compound I, which displays GI50 values of 30-80 nM against different ITD mutants and achieves selectivity over both FLT3 wt (8-fold) and cKIT kinase in the transformed BaF3 cells (>300-fold). I potently inhibits the proliferation of the FLT3-ITD-pos. acute myeloid leukemia cancer lines through suppression of the phosphorylation of FLT3 kinase and downstream signaling pathways, induction of apoptosis, and arresting the cell cycle into the G0/G1 phase. I also displays potent antiproliferative effect against FLT3-ITD-pos. patient primary cells, whereas it does not apparently affect FLT3 wt primary cells. In addition, it also exhibits a good therapeutic window to PBMC compared to PKC412. In the in vivo studies, I demonstrates favorable PK profiles and suppresses the tumor growth in the MV4-11 cell inoculated mouse xenograft model. In the experimental materials used by the author, we found 4,6-Dichloropyrimidine(cas: 1193-21-1Related Products of 1193-21-1)
4,6-Dichloropyrimidine(cas: 1193-21-1) is a member of organic chlorides. Almost all organochlorine compounds are synthesized. It is widely used as intermediates, solvents and pesticides of chemical synthetic products.Related Products of 1193-21-1
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia