Quantifying the CDK inhibitor VMY-1-103’s activity and tissue levels in an in vivo tumor model by LC-MS/MS and by MRI
| Autor: | Stanley T. Fricke, Emanuel F. Petricoin, Michael P. Lisanti, Yichien Lee, Angiela Sivakumar, Patricia Salinas, Aykut Üren, Richard Schlegel, Sana D. Karam, Sudeep Das, Sean S. Wang, Paul Sirajuddin, Bahram Moasser, Alpay Ozcan, Chris Albanese, Brian R. Rood, Venkata Mahidhar Yenugonda, Olga Rodriguez, Lymor Ringer, Yue Wang, Michael J. Pishvaian |
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| Rok vydání: | 2012 |
| Předmět: |
In vivo magnetic resonance spectroscopy
Biological Availability Antineoplastic Agents Pharmacology medulloblastoma CDK inhibitor Mice 03 medical and health sciences 0302 clinical medicine Tandem Mass Spectrometry Cyclin-dependent kinase In vivo Report MR-spectroscopy Animals Humans Distribution (pharmacology) Cerebellar Neoplasms Protein Kinase Inhibitors Molecular Biology 030304 developmental biology Dansyl Compounds 0303 health sciences prostate biology Adenine Cell Cycle Biological activity Cell Biology Cell cycle Magnetic Resonance Imaging animal models Cyclin-Dependent Kinases 3. Good health Bioavailability 030220 oncology & carcinogenesis biology.protein MRI Chromatography Liquid Developmental Biology |
| Zdroj: | Cell Cycle |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | The development of new small molecule-based therapeutic drugs requires accurate quantification of drug bioavailability, biological activity and treatment efficacy. Rapidly measuring these endpoints is often hampered by the lack of efficient assay platforms with high sensitivity and specificity. Using an in vivo model system, we report a simple and sensitive liquid chromatography-tandem mass spectrometry assay to quantify the bioavailability of a recently developed novel cyclin-dependent kinase inhibitor VMY-1-103, a purvalanol B-based analog whose biological activity is enhanced via dansylation. We developed a rapid organic phase extraction technique and validated wide and functional VMY-1-103 distribution in various mouse tissues, consistent with its enhanced potency previously observed in a variety of human cancer cell lines. More importantly, in vivo MRI and single voxel proton MR-Spectroscopy further established that VMY-1-103 inhibited disease progression and affected key metabolites in a mouse model of hedgehog-driven medulloblastoma. |
| Databáze: | OpenAIRE |
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