Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma

Autor:	Péter Bánhegyi, László Őrfi, Zoltán Horváth, Csaba Szántai-Kis, Mária Balogh, Bálint Szokol, Zsófia Czudor, Eszter Illyés, Judit Dobos, Márk Fábián, Nóra Breza, Sándor Boros, Anna Sipos, Péter Markó
Rok vydání:	2018
Předmět:	0301 basic medicine Pyrimidine Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Cell Cycle Proteins Polo-like kinase Protein Serine-Threonine Kinases Biochemistry PLK1 Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cyclin-dependent kinase Cell Line Tumor Proto-Oncogene Proteins Drug Discovery Humans Protein Kinase Inhibitors Molecular Biology Molecular Structure biology Kinase Organic Chemistry Cell cycle Cyclin-Dependent Kinase 9 enzymes and coenzymes (carbohydrates) Pyrimidines 030104 developmental biology chemistry Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein Molecular Medicine Cyclin-dependent kinase 9 biological phenomena cell phenomena and immunity Multiple Myeloma
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 28:769-773
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2018.01.002
Popis:	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).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47c0139cad5407f466b20ae41d91c700 https://doi.org/10.1016/j.bmcl.2018.01.002 Zobrazit plný text záznamu Full Text from ScienceDirect