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Exercise mimetic

An exercise mimetic is a drug that mimics some of the biological effects of physical exercise. Exercise is known to have an effect in preventing, treating, or ameliorating the effects of a variety of serious illnesses, including cancer, type 2 diabetes, cardiovascular disease, and psychiatric and neurological diseases such as Alzheimer's disease. As of 2021, no drug is known to have the same benefits.

Known biological targets affected by exercise have also been targets of drug discovery, with limited results. These known targets include:

TargetsDrug candidates
irisin
brain-derived neurotrophic factor
interleukin-6
peroxisome proliferator-activated receptor deltaGW501516
PPAR gamma coactivator 1-alpha
estrogen-related receptor γ/αGSK4716 SLU-PP-332
NFE2L2
Canonical transient receptor potential (TRPC) proteins
Myostatinmyostatin inhibitors

The majority of the effect of exercise in reducing cardiovascular and all-cause mortality cannot be explained via improvements in quantifiable risk factors, such as blood cholesterol. This further increases the challenge of developing an effective exercise mimetic. Moreover, even if a broad spectrum exercise mimetic were invented, it is not necessarily the case that its public health effects would be superior to interventions to increase exercise in the population.

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References

  1. Jang, Young Jin; Byun, Sanguine (31 December 2021). "Molecular targets of exercise mimetics and their natural activators". BMB Reports. 54 (12): 581–591. doi:10.5483/BMBRep.2021.54.12.151. ISSN 1976-6696. PMC 8728540. PMID 34814977. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540

  2. Febbraio, Mark A. (February 2017). "Health benefits of exercise — more than meets the eye!". Nature Reviews Endocrinology. 13 (2): 72–74. doi:10.1038/nrendo.2016.218. ISSN 1759-5037. PMID 28051119. S2CID 5824789. https://www.nature.com/articles/nrendo.2016.218

  3. Hawley, John A.; Joyner, Michael J.; Green, Daniel J. (February 2021). "Mimicking exercise: what matters most and where to next?". The Journal of Physiology. 599 (3): 791–802. doi:10.1113/JP278761. ISSN 0022-3751. PMC 7891316. PMID 31749163. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891316

  4. Jang, Young Jin; Byun, Sanguine (31 December 2021). "Molecular targets of exercise mimetics and their natural activators". BMB Reports. 54 (12): 581–591. doi:10.5483/BMBRep.2021.54.12.151. ISSN 1976-6696. PMC 8728540. PMID 34814977. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540

  5. Jang, Young Jin; Byun, Sanguine (31 December 2021). "Molecular targets of exercise mimetics and their natural activators". BMB Reports. 54 (12): 581–591. doi:10.5483/BMBRep.2021.54.12.151. ISSN 1976-6696. PMC 8728540. PMID 34814977. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540

  6. Jang, Young Jin; Byun, Sanguine (31 December 2021). "Molecular targets of exercise mimetics and their natural activators". BMB Reports. 54 (12): 581–591. doi:10.5483/BMBRep.2021.54.12.151. ISSN 1976-6696. PMC 8728540. PMID 34814977. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540

  7. Jang, Young Jin; Byun, Sanguine (31 December 2021). "Molecular targets of exercise mimetics and their natural activators". BMB Reports. 54 (12): 581–591. doi:10.5483/BMBRep.2021.54.12.151. ISSN 1976-6696. PMC 8728540. PMID 34814977. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540

  8. Jang, Young Jin; Byun, Sanguine (31 December 2021). "Molecular targets of exercise mimetics and their natural activators". BMB Reports. 54 (12): 581–591. doi:10.5483/BMBRep.2021.54.12.151. ISSN 1976-6696. PMC 8728540. PMID 34814977. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540

  9. Cento, Alessia S.; Leigheb, Massimiliano; Caretti, Giuseppina; Penna, Fabio (October 2022). "Exercise and Exercise Mimetics for the Treatment of Musculoskeletal Disorders". Current Osteoporosis Reports. 20 (5): 249–259. doi:10.1007/s11914-022-00739-6. hdl:2434/936387. PMID 35881303. https://doi.org/10.1007%2Fs11914-022-00739-6

  10. Jang, Young Jin; Byun, Sanguine (31 December 2021). "Molecular targets of exercise mimetics and their natural activators". BMB Reports. 54 (12): 581–591. doi:10.5483/BMBRep.2021.54.12.151. ISSN 1976-6696. PMC 8728540. PMID 34814977. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540

  11. Cento, Alessia S.; Leigheb, Massimiliano; Caretti, Giuseppina; Penna, Fabio (October 2022). "Exercise and Exercise Mimetics for the Treatment of Musculoskeletal Disorders". Current Osteoporosis Reports. 20 (5): 249–259. doi:10.1007/s11914-022-00739-6. hdl:2434/936387. PMID 35881303. https://doi.org/10.1007%2Fs11914-022-00739-6

  12. Numaga-Tomita, Takuro; Oda, Sayaka; Nishiyama, Kazuhiro; Tanaka, Tomohiro; Nishimura, Akiyuki; Nishida, Motohiro (March 2019). "TRPC channels in exercise-mimetic therapy". Pflügers Archiv - European Journal of Physiology. 471 (3): 507–517. doi:10.1007/s00424-018-2211-3. PMC 6515694. PMID 30298191. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515694

  13. Allen, David L.; Hittel, Dustin S.; McPherron, Alexandra C. (October 2011). "Expression and Function of Myostatin in Obesity, Diabetes, and Exercise Adaptation". Medicine and Science in Sports and Exercise. 43 (10): 1828–1835. doi:10.1249/MSS.0b013e3182178bb4. ISSN 0195-9131. PMC 3192366. PMID 21364474. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192366

  14. Hawley, John A.; Joyner, Michael J.; Green, Daniel J. (February 2021). "Mimicking exercise: what matters most and where to next?". The Journal of Physiology. 599 (3): 791–802. doi:10.1113/JP278761. ISSN 0022-3751. PMC 7891316. PMID 31749163. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891316

  15. Hawley, John A.; Joyner, Michael J.; Green, Daniel J. (February 2021). "Mimicking exercise: what matters most and where to next?". The Journal of Physiology. 599 (3): 791–802. doi:10.1113/JP278761. ISSN 0022-3751. PMC 7891316. PMID 31749163. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891316