title: Evaluating Chemical CDK Inhibitors as Cell Death Inducers.
abstract: The cell cycle of eukaryotic cells is regulated by a family of protein kinases called cyclin-dependent kinases (Cdks). We have reported the identification and biological characterization of a highly potent, small-molecule pan-Cdk inhibitor, which inhibited Cdk1, 2, 4, 5, 6, and 9 with equal potency in the nM range. This compound inhibited multiple events in the cell cycle and induced cell death in human cancer cell lines as well as in peripheral blood or purified resting lymphocytes ex vivo. We describe the materials and methods to determine antitumor efficacy in vivo xenograft models. Pharmacodynamic marker assays that have been performed using tumors and normal tissues are explained. Moreover, we briefly describe methods for determining the effects of chemical Cdk inhibitors on peripheral blood cells or lymphocytes ex vivo.
authors.affiliation: Taiho Pharmaceutical Co. Ltd., Tsukuba Research Center, 3 Okubo, Tsukuba, Ibaraki, 300-2611, Japan, hiroshi-hirai@taiho.co.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirai
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakatsuru
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D002453:Cell Cycle; D016923:Cell Death / Q000187:drug effects*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000737:chemistry*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D047428:Protein Kinase Inhibitors; D018844:Cyclin-Dependent Kinases