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

Paul Sirajuddin; Sudeep Das; Lymor Ringer; Olga C. Rodriguez; Angiela Sivakumar; Yi Chien Lee; Aykut Üren; Stanley T. Fricke; Brian Rood; Alpay Ozcan; Sean S. Wang; Sana Karam; Venkata Yenugonda; Patricia Salinas; Emanuel Petricoin; Michael Pishvaian; Michael P. Lisanti; Yue Wang; Richard Schlegel; Bahram Moasser; Chris Albanese

doi:10.4161/cc.21988

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

Paul Sirajuddin, Sudeep Das, Lymor Ringer, Olga C. Rodriguez, Angiela Sivakumar, Yi Chien Lee, Aykut Üren, Stanley T. Fricke, Brian Rood, Alpay Ozcan, Sean S. Wang, Sana Karam, Venkata Yenugonda, Patricia Salinas, Emanuel Petricoin, Michael Pishvaian, Michael P. Lisanti, Yue Wang, Richard Schlegel, Bahram MoasserChris Albanese

Research output: Contribution to journal › Article › peer-review

Abstract

The development of new small molecule-based therapeutic drugs requires accurate quantifcation of drug bioavailability, biological activity and treatment efcacy. Rapidly measuring these endpoints is often hampered by the lack of efcient assay platforms with high sensitivity and specifcity. 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 afected key metabolites in a mouse model of hedgehog-driven medulloblastoma. © 2012 Landes Bioscience.

Original language	English
Pages (from-to)	3801-3809
Number of pages	8
Journal	Cell Cycle
Volume	11
Issue number	20
DOIs	https://doi.org/10.4161/cc.21988
Publication status	Published - 15 Oct 2012

Keywords

Animal models
CDK inhibitor
Medulloblastoma
MR-Spectroscopy
MRI
Prostate
Tandem mass spectrometry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4161/cc.21988

http://www.landesbioscience.com/journals/cc/2012CC4324R.pdf?nocache=1708783945

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Sirajuddin, P., Das, S., Ringer, L., Rodriguez, O. C., Sivakumar, A., Lee, Y. C., Üren, A., Fricke, S. T., Rood, B., Ozcan, A., Wang, S. S., Karam, S., Yenugonda, V., Salinas, P., Petricoin, E., Pishvaian, M., Lisanti, M. P., Wang, Y., Schlegel, R., ... Albanese, C. (2012). 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. Cell Cycle, 11(20), 3801-3809. https://doi.org/10.4161/cc.21988

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title = "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",

abstract = "The development of new small molecule-based therapeutic drugs requires accurate quantifcation of drug bioavailability, biological activity and treatment efcacy. Rapidly measuring these endpoints is often hampered by the lack of efcient assay platforms with high sensitivity and specifcity. 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 afected key metabolites in a mouse model of hedgehog-driven medulloblastoma. {\textcopyright} 2012 Landes Bioscience.",

keywords = "Animal models, CDK inhibitor, Medulloblastoma, MR-Spectroscopy, MRI, Prostate, Tandem mass spectrometry",

author = "Paul Sirajuddin and Sudeep Das and Lymor Ringer and Rodriguez, {Olga C.} and Angiela Sivakumar and Lee, {Yi Chien} and Aykut {\"U}ren and Fricke, {Stanley T.} and Brian Rood and Alpay Ozcan and Wang, {Sean S.} and Sana Karam and Venkata Yenugonda and Patricia Salinas and Emanuel Petricoin and Michael Pishvaian and Lisanti, {Michael P.} and Yue Wang and Richard Schlegel and Bahram Moasser and Chris Albanese",

note = "P30 CA51008, NCI NIH HHS, United StatesR01CA129003, NCI NIH HHS, United States",

year = "2012",

month = oct,

day = "15",

doi = "10.4161/cc.21988",

language = "English",

volume = "11",

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Sirajuddin, P, Das, S, Ringer, L, Rodriguez, OC, Sivakumar, A, Lee, YC, Üren, A, Fricke, ST, Rood, B, Ozcan, A, Wang, SS, Karam, S, Yenugonda, V, Salinas, P, Petricoin, E, Pishvaian, M, Lisanti, MP, Wang, Y, Schlegel, R, Moasser, B & Albanese, C 2012, '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', Cell Cycle, vol. 11, no. 20, pp. 3801-3809. https://doi.org/10.4161/cc.21988

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T1 - 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

AU - Sirajuddin, Paul

AU - Das, Sudeep

AU - Ringer, Lymor

AU - Rodriguez, Olga C.

AU - Sivakumar, Angiela

AU - Lee, Yi Chien

AU - Üren, Aykut

AU - Fricke, Stanley T.

AU - Rood, Brian

AU - Ozcan, Alpay

AU - Wang, Sean S.

AU - Karam, Sana

AU - Yenugonda, Venkata

AU - Salinas, Patricia

AU - Petricoin, Emanuel

AU - Pishvaian, Michael

AU - Lisanti, Michael P.

AU - Wang, Yue

AU - Schlegel, Richard

AU - Moasser, Bahram

AU - Albanese, Chris

N1 - P30 CA51008, NCI NIH HHS, United StatesR01CA129003, NCI NIH HHS, United States

PY - 2012/10/15

Y1 - 2012/10/15

N2 - The development of new small molecule-based therapeutic drugs requires accurate quantifcation of drug bioavailability, biological activity and treatment efcacy. Rapidly measuring these endpoints is often hampered by the lack of efcient assay platforms with high sensitivity and specifcity. 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 afected key metabolites in a mouse model of hedgehog-driven medulloblastoma. © 2012 Landes Bioscience.

AB - The development of new small molecule-based therapeutic drugs requires accurate quantifcation of drug bioavailability, biological activity and treatment efcacy. Rapidly measuring these endpoints is often hampered by the lack of efcient assay platforms with high sensitivity and specifcity. 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 afected key metabolites in a mouse model of hedgehog-driven medulloblastoma. © 2012 Landes Bioscience.

KW - Animal models

KW - CDK inhibitor

KW - Medulloblastoma

KW - MR-Spectroscopy

KW - MRI

KW - Prostate

KW - Tandem mass spectrometry

U2 - 10.4161/cc.21988

DO - 10.4161/cc.21988

M3 - Article

C2 - 22983062

SN - 1538-4101

VL - 11

SP - 3801

EP - 3809

JO - Cell Cycle

JF - Cell Cycle

IS - 20

ER -

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

Abstract

Keywords

UN SDGs

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