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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.<ref name=Jang/><ref>{{cite journal |last1=Febbraio |first1=Mark A. |title=Health benefits of exercise — more than meets the eye! |journal=Nature Reviews Endocrinology |date=February 2017 |volume=13 |issue=2 |pages=72–74 |doi=10.1038/nrendo.2016.218 |url=https://www.nature.com/articles/nrendo.2016.218 |language=en |issn=1759-5037}}</ref><ref name=Hawley/> |
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.<ref name=Jang/><ref>{{cite journal |last1=Febbraio |first1=Mark A. |title=Health benefits of exercise — more than meets the eye! |journal=Nature Reviews Endocrinology |date=February 2017 |volume=13 |issue=2 |pages=72–74 |doi=10.1038/nrendo.2016.218 |url=https://www.nature.com/articles/nrendo.2016.218 |language=en |issn=1759-5037}}</ref><ref name=Hawley/> |
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Known biological targets affected by exercise have also been targets of [[drug discovery]], with limited results. These known targets include:<ref name=Jang/> |
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Known biological targets affected by exercise have also been targets of [[drug discovery]], with limited results. These targets include [[irisin]], [[brain-derived neurotrophic factor]], [[interleukin-6]], [[AMP-activated protein kinase]] (e.g. [[5-aminoimidazole-4-carboxamide ribonucleotide]]), [[peroxisome proliferator-activated receptor delta]] (e.g. [[GW501516]]), and [[estrogen-related receptor γ]] (e.g. [[GSK4716]]).<ref name=Jang>{{cite journal |last1=Jang |first1=Young Jin |last2=Byun |first2=Sanguine |title=Molecular targets of exercise mimetics and their natural activators |journal=BMB Reports |date=31 December 2021 |volume=54 |issue=12 |pages=581–591 |doi=10.5483/BMBRep.2021.54.12.151 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540/ |issn=1976-6696}}</ref> Other targets relevant to the musculoskeletal system are [[NFE2L2]] and [[PPARGC1A]].<ref>{{cite journal |last1=Cento |first1=Alessia S. |last2=Leigheb |first2=Massimiliano |last3=Caretti |first3=Giuseppina |last4=Penna |first4=Fabio |title=Exercise and Exercise Mimetics for the Treatment of Musculoskeletal Disorders |journal=Current Osteoporosis Reports |date=October 2022 |volume=20 |issue=5 |pages=249–259 |doi=10.1007/s11914-022-00739-6}}</ref> |
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!Targets |
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!Drug candidates |
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|[[irisin]]<ref name=Jang/> || |
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|[[brain-derived neurotrophic factor]]<ref name=Jang/> || |
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| [[interleukin-6]]<ref name=Jang/> || |
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|-[[AMP-activated protein kinase]] || [[5-aminoimidazole-4-carboxamide ribonucleotide]]<ref name=Jang/> |
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|[[peroxisome proliferator-activated receptor delta]]||[[GW501516]]<ref name=Jang/> |
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| [[PPARGC1A|PPAR gamma coactivator 1-alpha]]<ref name=Cento>{{cite journal |last1=Cento |first1=Alessia S. |last2=Leigheb |first2=Massimiliano |last3=Caretti |first3=Giuseppina |last4=Penna |first4=Fabio |title=Exercise and Exercise Mimetics for the Treatment of Musculoskeletal Disorders |journal=Current Osteoporosis Reports |date=October 2022 |volume=20 |issue=5 |pages=249–259 |doi=10.1007/s11914-022-00739-6}}</ref> || |
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|[[estrogen-related receptor γ]] || [[GSK4716]]<ref name=Jang>{{cite journal |last1=Jang |first1=Young Jin |last2=Byun |first2=Sanguine |title=Molecular targets of exercise mimetics and their natural activators |journal=BMB Reports |date=31 December 2021 |volume=54 |issue=12 |pages=581–591 |doi=10.5483/BMBRep.2021.54.12.151 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728540/ |issn=1976-6696}}</ref> |
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| [[NFE2L2]]<ref name=Cento/> || |
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| Canonical [[transient receptor potential]] (TRPC) proteins<ref>{{cite journal |last1=Numaga-Tomita |first1=Takuro |last2=Oda |first2=Sayaka |last3=Nishiyama |first3=Kazuhiro |last4=Tanaka |first4=Tomohiro |last5=Nishimura |first5=Akiyuki |last6=Nishida |first6=Motohiro |title=TRPC channels in exercise-mimetic therapy |journal=Pflügers Archiv - European Journal of Physiology |date=March 2019 |volume=471 |issue=3 |pages=507–517 |doi=10.1007/s00424-018-2211-3}}</ref> || |
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| [[Myostatin]] || [[myostatin inhibitors]]<ref>{{cite journal |last1=Allen |first1=David L. |last2=Hittel |first2=Dustin S. |last3=McPherron |first3=Alexandra C. |title=Expression and Function of Myostatin in Obesity, Diabetes, and Exercise Adaptation |journal=Medicine and science in sports and exercise |date=October 2011 |volume=43 |issue=10 |pages=1828–1835 |doi=10.1249/MSS.0b013e3182178bb4 |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192366/|issn=0195-9131}}</ref> |
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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.<ref name=Hawley/> 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.<ref name=Hawley/> |
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.<ref name=Hawley/> 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.<ref name=Hawley/> |
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Anexercise 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]
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]
