Yuan, Kai; Ji, Minghui; Xie, Shengnan; Qiu, Zhixia; Chen, Weijiao; Min, Wenjian; Xia, Fei; Zheng, Mingming; Wang, Xiao; Li, Jiaxing; Hou, Yi; Kuang, Wenbin; Wang, Liping; Gu, Wanjian; Li, Zhiyu; Yang, Peng published an article in 2022. The article was titled 《Discovery of Dual CDK6/PIM1 Inhibitors with a Novel Structure, High Potency, and Favorable Druggability for the Treatment of Acute Myeloid Leukemia》, and you may find the article in Journal of Medicinal Chemistry.Category: pyrimidines The information in the text is summarized as follows:
Nowadays, the simultaneous inhibition of two or more pathways plays an increasingly important role in cancer treatment due to the complex and diverse pathogenesis of cancer, and the combination of the cyclin-dependent kinase 6 (CDK6) inhibitor and PIM1 inhibitor was found to generate synergistic effects in acute myeloid leukemia (AML) treatment. Therefore, we discovered a novel lead 1 targeting CDK6/PIM1 via pharmacophore-based and structure-based virtual screening, synthesized five different series of new derivates, and obtained a potent and balanced dual CDK6/PIM1 inhibitor 51 (I), which showed high kinase selectivity. Meanwhile, 51 displayed an excellent safety profile and great pharmacokinetic properties. Furthermore, 51 displayed stronger potency in reducing the burden of AML than palbociclib and SMI-4a in vivo. In summary, we offered a new direction for AML treatment and provided a great lead compound for AML preclin. studies. The experimental process involved the reaction of 2,4-Dichloropyrimidine(cas: 3934-20-1Category: pyrimidines)
2,4-Dichloropyrimidine(cas: 3934-20-1) 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.Category: pyrimidines
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia