Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging
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 of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach f...
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doaj-0fdb69ea61d041d08cbf8b34fb7a06592020-11-25T00:06:32ZengHindawi LimitedJournal of Oncology1687-84501687-84692009-01-01200910.1155/2009/106378106378Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor ImagingFranziska Graf0Lena Koehler1Torsten Kniess2Frank Wuest3Birgit Mosch4Jens Pietzsch5Research Center Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, GermanyResearch Center Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, GermanyResearch Center Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, GermanyDepartment of Oncologic Imaging, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton AB, T6G 1Z2, CanadaResearch Center Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, GermanyResearch Center Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, GermanyThe 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 of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach for cancer therapy. We hypothesized that appropriately radiolabeled Cdk4 inhibitors are suitable probes for tumor imaging and may be helpful studying cell proliferation processes in vivo by positron emission tomography. Herein, we report the synthesis and biological, biochemical, and radiopharmacological characterizations of two I124-labeled small molecule Cdk4 inhibitors (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-yl-phenylamino)-8H-pyrido[2,3-d]-pyrimidin-7-one (CKIA) and 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl)-pyridin-2-yl-amino)-8H-pyrido[2,3-d]pyrimidin-7-one (CKIB)). Our data demonstrate a defined and specific inhibition of tumor cell proliferation through CKIA and CKIB by inhibition of the Cdk4/pRb/E2F pathway emphasizing potential therapeutic benefit of CKIA and CKIB. Furthermore, radiopharmacological properties of [I124]CKIA and [I124]CKIB observed in human tumor cells are promising prerequisites for in vivo biodistribution and imaging studies.http://dx.doi.org/10.1155/2009/106378 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Franziska Graf Lena Koehler Torsten Kniess Frank Wuest Birgit Mosch Jens Pietzsch |
spellingShingle |
Franziska Graf Lena Koehler Torsten Kniess Frank Wuest Birgit Mosch Jens Pietzsch Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging Journal of Oncology |
author_facet |
Franziska Graf Lena Koehler Torsten Kniess Frank Wuest Birgit Mosch Jens Pietzsch |
author_sort |
Franziska Graf |
title |
Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging |
title_short |
Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging |
title_full |
Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging |
title_fullStr |
Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging |
title_full_unstemmed |
Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging |
title_sort |
cell cycle regulating kinase cdk4 as a potential target for tumor cell treatment and tumor imaging |
publisher |
Hindawi Limited |
series |
Journal of Oncology |
issn |
1687-8450 1687-8469 |
publishDate |
2009-01-01 |
description |
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 of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach for cancer therapy. We hypothesized that appropriately radiolabeled Cdk4 inhibitors are suitable probes for tumor imaging and may be helpful studying cell proliferation processes in vivo by positron emission tomography. Herein, we report the synthesis and biological, biochemical, and radiopharmacological characterizations of two I124-labeled small molecule Cdk4 inhibitors (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-yl-phenylamino)-8H-pyrido[2,3-d]-pyrimidin-7-one (CKIA) and 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl)-pyridin-2-yl-amino)-8H-pyrido[2,3-d]pyrimidin-7-one (CKIB)). Our data demonstrate a defined and specific inhibition of tumor cell proliferation through CKIA and CKIB by inhibition of the Cdk4/pRb/E2F pathway emphasizing potential therapeutic benefit of CKIA and CKIB. Furthermore, radiopharmacological properties of [I124]CKIA and [I124]CKIB observed in human tumor cells are promising prerequisites for in vivo biodistribution and imaging studies. |
url |
http://dx.doi.org/10.1155/2009/106378 |
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