Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced Obesity in Vivo Mouse Model

Author:

Fromont Christophe1,Atzori Alessio1,Kaur Divneet1,Hashmi Lubna1,Greco Graziella2,Cabanillas Alejandro2,Nguyen Huy Van2ORCID,Jones D. Heulyn3,Garzón Miguel3,Varela Ana3,Stevenson Brett4,Iacobini Greg P.4,Lenoir Marc5,Rajesh Sundaresan5,Box Clare5,Kumar Jitendra6,Grant Paige6,Novitskaya Vera5,Morgan Juliet4,Sorrell Fiona J.7,Redondo Clara7,Kramer Andreas8,Harris C. John9,Leighton Brendan10,Vickers Steven P.11,Cheetham Sharon C.11,Kenyon Colin12,Grabowska Anna M.13,Overduin Michael6,Berditchevski Fedor5,Weston Chris J.1415,Knapp Stefan8ORCID,Fischer Peter M.1ORCID,Butterworth Sam3ORCID

Affiliation:

1. Centre for Biomolecular Sciences and School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K.

2. School of Pharmacy, College of Medical and Dental Sciences, University of Birmingham, Edgbaston B15 2TT, U.K.

3. Division of Pharmacy and Optometry, School of Health Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester M13 9PL, U.K.

4. Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GF, U.K.

5. Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.

6. Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2H7, Canada

7. Structural Genomics Consortium and Target Discovery Institute, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, U.K.

8. Structural Genomics Consortium and Buchmann Institute for Molecular Life Sciences, Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Straße 9, 60438 Frankfurt am Main, Germany

9. CJH Consultants, Ford Cottage, South Weirs, Burley Road, Brockenhurst, Hants SO42 7UQ, U.K.

10. The Research Network, IPC 600 Discovery Park, Ramsgate Road, Sandwich CT13 9NJ, U.K.

11. RenaSci Limited, BioCity, Pennyfoot Street, Nottingham NG1 1GF, U.K.

12. DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Molecular and Cellular Biology, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa

13. Ex Vivo Cancer Pharmacology Centre of Excellence, Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham NG7 2RD, U.K.

14. Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, U.K.

15. NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, B15 2TT, U.K.

Funder

Medical Research Council

Wellcome Trust

Publisher

American Chemical Society (ACS)

Subject

Drug Discovery,Molecular Medicine

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