title: Tricyclic Benzo[cd]azulenes selectively inhibit activities of Pim kinases and restrict growth of Epstein-Barr virus-transformed cells.
abstract: Oncogenic Pim family kinases are often overexpressed in human hematopoietic malignancies as well as in solid tumours. These kinases contribute to tumorigenesis by promoting cell survival and by enhancing resistance against chemotherapy and radiation therapy. Furthermore, we have recently shown that they increase the metastatic potential of adherent cancer cells. Here we describe identification of tricyclic benzo[cd]azulenes and their derivatives as effective and selective inhibitors of Pim kinases. These compounds inhibit Pim autophosphorylation and abrogate the anti-apoptotic effects of Pim kinases. They also reduce cancer cell motility and suppress proliferation of lymphoblastoid cell lines infected and immortalized by the Epstein-Barr virus. Thus, these novel Pim-selective inhibitors provide promising compounds for both research and therapeutic purposes.
authors: Division of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Helsinki, Finland.
authors: Alexandros
authors: A
authors: Kiriazis
authors: Riitta L
authors: RL
authors: Vahakoski
authors: Niina M
authors: NM
authors: Santio
authors: Ralica
authors: R
authors: Arnaudova
authors: Sini K
authors: SK
authors: Eerola
authors: Eeva-Marja
authors: EM
authors: Rainio
authors: Ingo B
authors: IB
authors: Aumüller
authors: Jari
authors: J
authors: Yli-Kauhaluoma
authors: Päivi J
authors: PJ
authors: Koskinen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052176:Azulenes / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects* / Q000821:virology; D010766:Phosphorylation / Q000187:drug effects; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D052176:Azulenes; D051573:Proto-Oncogene Proteins c-pim-1; C406031:proto-oncogene proteins pim