Authors

Paul Sirajuddin, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Sudeep Das, Department of Chemistry, Georgetown University
Lymor Ringer, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Olga C Rodriguez, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Angiela Sivakumar, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Yi-Chien Lee, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Aykut Üren, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Stanley T Fricke, Children's National Medical Center, Washington, DC
Brian Rood, Children's National Medical Center, Washington, DC
Alpay Ozcan, Department of Physics, Virginia Tech.
Sean S Wang, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Sana Karam, Department of Radiation Biology, Georgetown University Medical Center
Venkata Yenugonda, Drug Discovery Program, Georgetown University Medical Center,
Patricia Salinas, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Emanuel Petricoin, Center for Applied Proteomics and Molecular Medicine, School of Systems Biology, George Mason University
Michael Pishvaian, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center
Michael P Lisanti, Department Stem Cell Biology, Kimmel Cancer Center, Thomas Jeferson UniversityFollow
Yue Wang, Department of Physics, Virginia Tech.; Bradley Department of Electrical and Computer Engineering, Virginia Tech.
Richard Schlegel, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center; Department of Pathology; Georgetown University Medical Center
Bahram Moasser, Department of Chemistry, Georgetown University
Chris Albanese, Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center; Department of Pathology, Georgetown University Medical Center

Document Type

Article

Publication Date

10-15-2012

Comments

This article has been peer reviewed. It was published in Cell Cycle:

Volume 11, Issue 20, 15 October 2012, Pages 3801-3809.

The published version is available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495823/. DOI: 10.4161/cc.21988. Copyright © 2012 Landes Bioscience.

Abstract

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.

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