Abstract
The importance of circadian biology has rarely been considered in pre-clinical studies, and even more when translating to the bedside. Circadian biology is becoming a critical factor for improving drug efficacy and diminishing drug toxicity. Indeed, there is emerging evidence showing that some drugs are more effective at nighttime than daytime, whereas for others it is the opposite. This suggests that the biology of the target cell will determine how an organ will respond to a drug at a specific time of the day, thus modulating pharmacodynamics. Thus, it is now time that circadian factors become an integral part of translational research. In this Perspective, Cederroth et al. discuss the importance of considering circadian mechanisms when performing preclinical research with the aim of translating the findings to the clinic. By integrating chronopharmacology into clinical practice, it may be possible to minimize adverse side effects and maximize therapeutic efficacy, ultimately improving patient care.
Original language | English (US) |
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Pages (from-to) | 238-250 |
Number of pages | 13 |
Journal | Cell Metabolism |
Volume | 30 |
Issue number | 2 |
DOIs | |
State | Published - Aug 6 2019 |
Funding
Research in the Canlon lab is funded by Communication Disorders of the National Institutes of Health R21DC013172 and 1R56DC016415-01 , the Swedish Medical Research Council K2014-99X-22478-01-3 , the Knut and Alice Wallenberg Foundation (B.C., # KAW2008 ), the Karolinska Institutet , Tysta Skolan , Hörselforskningsfonden , Magnus Bergvalls , and the EU (H2020-MSCA-ITN, ESIT, C.R.C., project #722046). B.C. and C.R.C. also received funding from the Office of the Assistant Secretary of Defense for Health Affairs , through the Neurosensory and Rehabilitation program, under award no. W81XWH-16-1-0032. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. Research in the Helfrich-Förster lab is funded by the German Research Foundation (DFG; FO207/15-1 ) and the EU ( H2020-MSCA-ITN-2017 , CINCHRON, project #765937). C.B.G. was supported by NIH grant R35 GM127122 . J.S.T. is an Investigator in the Howard Hughes Medical Institute. M.H.H. was funded by the UK Medical Research Council , U.K. ( MC_U105170643 ). Research in the U.A. lab is funded by the Swiss National Science Foundation ( SNF 310030_184667/1 ) and the Velux Foundation (no. 995 ). F.L. was funded by CRUK ( C53561/A 19933 ), MRC ( MR/M013170 ), Philips Respironics (USA), the McGrath Family , and Ramsay-Generale-de-Sante (Fr). J.B.’s work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK090625 , R01DK100814 , R01DK11301 , and R01DK050203 ; the National Institute on Aging grant P01AG011412 ; the Chicago Biomedical Consortium S-007 ; and the University of Chicago Diabetes Research and Training Center grant P60DK020595 . F.G. received support from the Institute for Molecular Bioscience , The University of Queensland. S.A.B. is supported by the Swiss National Science Foundation, the Velux Foundation, and the Human Frontiers Science Program . M.Y. is supported by a grant from the National Institutes of Health ( GM054339 ). Research in the Canlon lab is funded by Communication Disorders of the National Institutes of Health R21DC013172 and 1R56DC016415-01, the Swedish Medical Research Council K2014-99X-22478-01-3, the Knut and Alice Wallenberg Foundation (B.C. #KAW2008), the Karolinska Institutet, Tysta Skolan, H?rselforskningsfonden, Magnus Bergvalls, and the EU (H2020-MSCA-ITN, ESIT, C.R.C. project #722046). B.C. and C.R.C. also received funding from the Office of the Assistant Secretary of Defense for Health Affairs, through the Neurosensory and Rehabilitation program, under award no. W81XWH-16-1-0032. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. Research in the Helfrich-F?rster lab is funded by the German Research Foundation (DFG; FO207/15-1) and the EU (H2020-MSCA-ITN-2017, CINCHRON, project #765937). C.B.G. was supported by NIH grant R35 GM127122. J.S.T. is an Investigator in the Howard Hughes Medical Institute. M.H.H. was funded by the UK Medical Research Council, U.K. (MC_U105170643). Research in the U.A. lab is funded by the Swiss National Science Foundation (SNF 310030_184667/1) and the Velux Foundation (no. 995). F.L. was funded by CRUK (C53561/A 19933), MRC (MR/M013170), Philips Respironics (USA), the McGrath Family, and Ramsay-Generale-de-Sante (Fr). J.B.?s work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01DK090625, R01DK100814, R01DK11301, and R01DK050203; the National Institute on Aging grant P01AG011412; the Chicago Biomedical Consortium S-007; and the University of Chicago Diabetes Research and Training Center grant P60DK020595. F.G. received support from the Institute for Molecular Bioscience, The University of Queensland. S.A.B. is supported by the Swiss National Science Foundation, the Velux Foundation, and the Human Frontiers Science Program. M.Y. is supported by a grant from the National Institutes of Health (GM054339). All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication. J.D.-J. is an employee and shareholder of Sensorion. All other authors declare that they have no competing financial interests. J.S.T. is a co-founder and scientific advisory board member of Reset Therapeutics.
Keywords
- ADME
- chronotherapy
- circadian biology
- clock genes
- drug metabolism
- translation
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cell Biology