AdipoRon
{{short description|Chemical compound}}
{{Drugbox
| Verifiedfields =
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| IUPAC_name = 2-(4-Benzoylphenoxy)-N-(1-benzylpiperidin-4-yl)acetamide
| image = AdipoRon.svg
| width = 250
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| routes_of_administration = Oral
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| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 924416-43-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = ND7UVH6GKJ
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| ATC_prefix = None
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| PubChem = 16307093
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| ChemSpiderID = 11029953
| C=27 | H=28 | N=2 | O=3
| smiles = C1CN(CCC1NC(=O)COC2=CC=C(C=C2)C(=O)C3=CC=CC=C3)CC4=CC=CC=C4
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AdipoRon is a selective, orally active, synthetic small-molecule agonist of the adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2) (Kd = 1.8 μM and 3.1 μM, respectively).{{cite journal | vauthors = Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, Yamaguchi M, Tanabe H, Kimura-Someya T, Shirouzu M, Ogata H, Tokuyama K, Ueki K, Nagano T, Tanaka A, Yokoyama S, Kadowaki T | display-authors = 6 | title = A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity | journal = Nature | volume = 503 | issue = 7477 | pages = 493–499 | date = November 2013 | pmid = 24172895 | doi = 10.1038/nature12656 | s2cid = 4447039 | bibcode = 2013Natur.503..493O }}{{cite journal | vauthors = Holland WL, Scherer PE | title = Cell Biology. Ronning after the adiponectin receptors | journal = Science | volume = 342 | issue = 6165 | pages = 1460–1461 | date = December 2013 | pmid = 24357309 | pmc = 4084614 | doi = 10.1126/science.1249077 | bibcode = 2013Sci...342.1460H }} It activates AMPK and PPARα signaling and ameliorates insulin resistance, dyslipidemia, and glucose intolerance in db/db mice (an animal model for type II diabetes and obesity). Moreover, AdipoRon has been found to extend the lifespans of db/db mice fed a high-fat diet, as well as improve exercise endurance.{{cite journal | vauthors = Okada-Iwabu M, Iwabu M, Ueki K, Yamauchi T, Kadowaki T | title = Perspective of Small-Molecule AdipoR Agonist for Type 2 Diabetes and Short Life in Obesity | journal = Diabetes & Metabolism Journal | volume = 39 | issue = 5 | pages = 363–372 | date = October 2015 | pmid = 26566493 | pmc = 4641965 | doi = 10.4093/dmj.2015.39.5.363 }} The compound was discovered by Japanese researchers in 2013 via screening of a compound library, and is the first orally active, small-molecule agonist of the adiponectin receptors to be identified.
Adiponectin receptor agonists such as AdipoRon have attracted interest as potential therapies for obesity, diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and a panoply of other conditions. In addition, adiponectin has recently been elucidated to mediate the antidepressant, anxiolytic, and neurogenic effects of physical exercise.{{cite journal | vauthors = Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, Xu A, So KF | display-authors = 6 | title = Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 44 | pages = 15810–15815 | date = November 2014 | pmid = 25331877 | pmc = 4226125 | doi = 10.1073/pnas.1415219111 | doi-access = free | bibcode = 2014PNAS..11115810Y }}{{cite journal | vauthors = Nicolas S, Veyssière J, Gandin C, Zsürger N, Pietri M, Heurteaux C, Glaichenhaus N, Petit-Paitel A, Chabry J | display-authors = 6 | title = Neurogenesis-independent antidepressant-like effects of enriched environment is dependent on adiponectin | journal = Psychoneuroendocrinology | volume = 57 | pages = 72–83 | date = July 2015 | pmid = 25889841 | doi = 10.1016/j.psyneuen.2015.03.017 | s2cid = 20252349 }}{{cite journal | vauthors = Li A, Yau SY, Machado S, Yuan TF, So KF | title = Adult Neurogenic and Antidepressant Effects of Adiponectin: A Potential Replacement for Exercise? | journal = CNS & Neurological Disorders Drug Targets | volume = 14 | issue = 9 | pages = 1129–1144 | year = 2015 | pmid = 26556072 | doi = 10.2174/1871527315666151111125533 }} Dysregulation of adiponectin expression has also been implicated in the pathology of mood disorders, anxiety disorders, eating disorders, neurodegenerative disorders, and various other neuropsychiatric disorders.{{cite journal | vauthors = Wędrychowicz A, Zając A, Pilecki M, Kościelniak B, Tomasik PJ | title = Peptides from adipose tissue in mental disorders | journal = World Journal of Psychiatry | volume = 4 | issue = 4 | pages = 103–111 | date = December 2014 | pmid = 25540725 | pmc = 4274582 | doi = 10.5498/wjp.v4.i4.103 | doi-access = free }} Also, it has been determined that exercise improves insulin resistance via activation of AdipoR1.{{cite journal | vauthors = Cho JK, Kim SU, Hong HR, Yoon JH, Kang HS | title = Exercise Training Improves Whole Body Insulin Resistance via Adiponectin Receptor 1 | journal = International Journal of Sports Medicine | volume = 36 | issue = 13 | pages = e24–e30 | date = November 2015 | pmid = 26528942 | doi = 10.1055/s-0035-1559715 | s2cid = 23387523 }} As such, adiponectin receptor agonists are a highly interesting therapeutic target for a variety of different conditions. Moreover, it has been suggested they could potentially be used as a substitute for exercise to achieve similar physical and mental health benefits.{{cite journal | vauthors = Yau SY, Li A, Xu A, So KF | title = Fat cell-secreted adiponectin mediates physical exercise-induced hippocampal neurogenesis: an alternative anti-depressive treatment? | journal = Neural Regeneration Research | volume = 10 | issue = 1 | pages = 7–9 | date = January 2015 | pmid = 25788905 | pmc = 4357120 | doi = 10.4103/1673-5374.150637 | doi-access = free }}
In 2016, the University of Tokyo announced that it would launch an investigation into claims of fabrication of AdipoR1, AdipoR2, and AdipoRon identification data, as accused by an anonymous person/group called Ordinary_researchers.{{cite web | url = https://www.science.org/content/article/university-tokyo-investigate-data-manipulation-charges-against-six-prominent-research | title = University of Tokyo to investigate data manipulation charges against six prominent research groups | work = ScienceInsider | vauthors = Normile D | date = 30 September 2016 }}