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Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation by Pal, Akos; Asad, Yasmin; Ruddle, Ruth; Henley, Alan T.; Swales, Karen; Decordova, Shaun; Eccles, Suzanne A .; Collins, Ian; Garrett, Michelle D.; De Bono, Johann; Banerji, Udai; Raynaud, Florence I. is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
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## Introduction To generate biomarkers of target engagement or predictive response for multi-target drugs is challenging. One such compound is the multi-AGC kinase inhibitor AT13148. Metabolic signatures of selective signal transduction inhibitors identified in preclinical models have previously been confirmed in early clinical studies. This study explores whether metabolic signatures could be used as biomarkers for the multi-AGC kinase inhibitor AT13148. ## Objectives To identify metabolomic changes of biomarkers of multi-AGC kinase inhibitor AT13148 in cells, xenograft / mouse models and in patients in a Phase I clinical study. ## Methods HILIC LC–MS/MS methods and Biocrates AbsoluteIDQTM p180 kit were used for targeted metabolomics; followed by multivariate data analysis in SIMCA and statistical analysis in Graphpad. Metaboanalyst and String were used for network analysis. ## Results BT474 and PC3 cells treated with AT13148 affected metabolites which are in a gene protein metabolite network associated with Nitric oxide synthases (NOS). In mice bearing the human tumour xenografts BT474 and PC3, AT13148 treatment did not produce a common robust tumour specific metabolite change. H
Who reads Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Pal, Akos; Asad, Yasmin; Ruddle, Ruth; Henley, Alan T.; Swales, Karen; Decordova, Shaun; Eccles, Suzanne A .; Collins, Ian; Garrett, Michelle D.; De Bono, Johann; Banerji, Udai; Raynaud, Florence I.
- Publisher
- Springer; Springer-Verlag; Springer Verlag; Springer Science and Business Media LLC (ISSN 1573-3882)
- Published
- 2020
- Language
- EN
- ISBN
- 9781130602005
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)