Discovery of methyl 3-((2-((1-(dimethylglycyl)-5-methoxyindolin-6-yl)amino)-5-(trifluoro-methyl) pyrimidin-4-yl)amino)thiophene-2-carboxylate as a potent and selective polo-like kinase 1 (PLK1) inhibitor for combating hepatocellular carcinoma

Autor:	Jiaji Zhong, Yunzhan Li, Li Li, Xianming Deng, Zheng Wang, Huiying Huang, Zhang Baoding, Qingyan Xu, Guyue Chen, Liu Shuang, Deng Zhou
Rok vydání:	2020
Předmět:	Carcinoma Hepatocellular Antineoplastic Agents Apoptosis Cell Cycle Proteins Thiophenes Polo-like kinase Protein Serine-Threonine Kinases 01 natural sciences PLK1 Mice 03 medical and health sciences Proto-Oncogene Proteins Drug Discovery medicine Animals Humans Structure–activity relationship Protein Kinase Inhibitors IC50 Cell Proliferation 030304 developmental biology Pharmacology 0303 health sciences 010405 organic chemistry Chemistry Kinase Liver Neoplasms Organic Chemistry Hep G2 Cells General Medicine Biochemical Activity medicine.disease Xenograft Model Antitumor Assays 0104 chemical sciences Thiophene-2-carboxylate G2 Phase Cell Cycle Checkpoints Biochemistry Drug Design Hepatocellular carcinoma M Phase Cell Cycle Checkpoints
Zdroj:	European Journal of Medicinal Chemistry. 206:112697
ISSN:	0223-5234
DOI:	10.1016/j.ejmech.2020.112697
Popis:	Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide and targeted therapeutics exhibit limited success. Polo-like kinase 1 (PLK1), a Ser/Thr kinase, plays a pivotal role in cell-cycle regulation and is considered a promising target in HCC. Here, via structural optimization using both biochemical kinase assays and cellular antiproliferation assays, we discovered a potent and selective PLK1 kinase inhibitor, compound 31. Compound 31 exhibited biochemical activity with IC50 of
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab771ef05bcd248835b41f71111be2d9 https://doi.org/10.1016/j.ejmech.2020.112697 Zobrazit plný text záznamu Full Text from ScienceDirect