Document Type
Article
Publication Date
10-15-2012
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.
Recommended Citation
Sirajuddin, Paul; Das, Sudeep; Ringer, Lymor; Rodriguez, Olga C; Sivakumar, Angiela; Lee, Yi-Chien; Üren, Aykut; Fricke, Stanley T; Rood, Brian; Ozcan, Alpay; Wang, Sean S; Karam, Sana; Yenugonda, Venkata; Salinas, Patricia; Petricoin, Emanuel; Pishvaian, Michael; Lisanti, Michael P; Wang, Yue; Schlegel, Richard; Moasser, Bahram; and Albanese, Chris, "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." (2012). Kimmel Cancer Center Faculty Papers. Paper 37.
https://jdc.jefferson.edu/kimmelccfp/37
PubMed ID
22983062
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.