Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging

摘要: The cyclin-dependent kinase (Cdk)-cyclin D/retinoblastoma (pRb)/E2F cascade, which controls the G1/S transition of cell cycle, has been found to be altered in many neoplasias. Inhibition this pathway by using, for example, selective Cdk4 inhibitors suggested a promising approach cancer therapy. We hypothesized that appropriately radiolabeled are suitable probes tumor imaging and may helpful studying proliferation processes vivo positron emission tomography. Herein, we report synthesis biological, biochemical, radiopharmacological characterizations two -labeled small molecule (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-yl-phenylamino)-8H-pyrido[2,3-]-pyrimidin-7-one (CKIA) 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl)-pyridin-2-yl-amino)-8H-pyrido[2,3-]pyrimidin-7-one (CKIB)). Our data demonstrate defined specific inhibition through CKIA CKIB Cdk4/pRb/E2F emphasizing potential therapeutic benefit CKIB. Furthermore, properties observed human cells prerequisites biodistribution studies.