具有强效CDK9抑制活性用于治疗骨髓瘤的新型化合物。
Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma.
作者信息
Czudor Zsófia, Balogh Mária, Bánhegyi Péter, Boros Sándor, Breza Nóra, Dobos Judit, Fábián Márk, Horváth Zoltán, Illyés Eszter, Markó Péter, Sipos Anna, Szántai-Kis Csaba, Szokol Bálint, Őrfi László
机构信息
Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9, 1092 Budapest, Hungary.
Vichem Chemie Research Ltd., Herman Ottó u. 15., 1022 Budapest, Hungary.
出版信息
Bioorg Med Chem Lett. 2018 Feb 15;28(4):769-773. doi: 10.1016/j.bmcl.2018.01.002. Epub 2018 Jan 2.
Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).
细胞周期蛋白依赖性激酶（CDKs）和波罗蛋白样激酶（PLKs）在细胞周期调控中起关键作用。我们研究的最初目的是进一步开发我们最近发现的波罗蛋白样激酶1（PLK1）抑制剂。围绕最初的活性化合物合成了一系列新的2,4-二取代嘧啶衍生物，但它们的PLK1抑制活性非常差。然而，这些新化合物显示出纳摩尔级的CDK9抑制活性，并且对多发性骨髓瘤细胞系（RPMI-8226）具有非常好的抗增殖作用。
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