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.[2][3][1]

Known biological targets affected by exercise have also been targets of drug discovery, with limited results. These known targets include:[2]

Targets Drug candidates
irisin[2]
brain-derived neurotrophic factor[2] ACD-856 (PAM of BDNF receptor TrkB)[4]
interleukin-6[2]
peroxisome proliferator-activated receptor delta GW501516[2]
PPAR gamma coactivator 1-alpha[5]
estrogen-related receptor γ/α GSK4716[2] SLU-PP-332
NFE2L2[5]
Canonical transient receptor potential (TRPC) proteins[6]
Myostatin myostatin inhibitors[7]

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.[1] 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.[1]

Exogenous administration of cardiotrophin-1 (CT-1) in rodents has been found to mimic the beneficial effects of exercise on the heart in a rodent model of severe right-sided heart failure.[8][9][10][11][12] CT-1 is under formal development for the treatment of reperfusion injury.[13] It is or was also under development for treatment of acute kidney injury, diabetes mellitus, ischemia, liver failure, and obesity, but no recent development for these indications has been reported.[13]

References

  1. ^ a b c d 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.
  2. ^ a b c d e f g h 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.
  3. ^ 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.
  4. ^ Wang, Dong; Lang, Zhi‐Chen; Wei, Shi‐Nan; Wang, Wei; Zhang, Hao (2024-05-02). "Targeting brain‐derived neurotrophic factor in the treatment of neurodegenerative diseases: A review". Neuroprotection. 2 (2): 67–78. doi:10.1002/nep3.43. ISSN 2770-7296. PMC 12486910. PMID 41383700. Archived from the original on 2025-06-11.
  5. ^ a b 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. PMC 9522759. PMID 35881303.
  6. ^ 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.
  7. ^ 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.
  8. ^ Zelt JG, Chaudhary KR, Cadete VJ, Mielniczuk LM, Stewart DJ (May 2019). "Medical Therapy for Heart Failure Associated With Pulmonary Hypertension". Circ Res. 124 (11): 1551–1567. doi:10.1161/CIRCRESAHA.118.313650. PMID 31120820.
  9. ^ Abdul-Ghani M, Suen C, Jiang B, Deng Y, Weldrick JJ, Putinski C, Brunette S, Fernando P, Lee TT, Flynn P, Leenen FH, Burgon PG, Stewart DJ, Megeney LA (October 2017). "Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart". Cell Res. 27 (10): 1195–1215. doi:10.1038/cr.2017.87. PMC 5630684. PMID 28785017.
  10. ^ How to trick your heart into thinking you exercise, retrieved 15 March 2026
  11. ^ Watson, Sara Kiley (10 August 2017). "This protein makes your heart fit without actually exercising it". Popular Science. Retrieved 15 March 2026.
  12. ^ Buguliskis, Jeffrey S. (8 August 2017). "Fooling the Heart to Be Healthier". GEN - Genetic Engineering and Biotechnology News. Retrieved 15 March 2026.
  13. ^ a b "Digna Biotech/Biotecnol". AdisInsight. 2 October 2021. Retrieved 15 March 2026.
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