SRT1720

SRT1720 is an experimental drug that was studied by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuin subtype SIRT1. The compound has been studied in animals, but safety and efficacy in humans have not been established.

SRT1720
Identifiers
PubChem CID
IUPHAR/BPS
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H23N7OS
Molar mass469.57 g·mol−1
3D model (JSmol)
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Animal research

In animal models of obesity and diabetes SRT1720 was found to improve insulin sensitivity and lower plasma glucose levels in fat, muscle and liver tissue, and increase mitochondrial and metabolic function.[1] In mice rendered obese and diabetic by feeding a high-fat, high-sugar diet, a study performed at the National Institute of Aging found that feeding chow infused with the highest dose of SRT1720 beginning at one year of age increased mean lifespan by 18%, and maximum lifespan by 5%, as compared to other short-lived obese, diabetic mice; however, treated animals still lived substantially shorter lives than normal-weight mice fed normal chow with no drug.[2] In a later study, SRT1720 increased mean lifespan of obese, diabetic mice by 21.7%, similar to the earlier study, but there was no effect on maximum lifespan in this study.[3] In normal-weight mice fed a standard rodent diet, SRT1720 increased mean lifespan by just 8.8%, and again had no effect on maximum lifespan.[3]

Since the discovery of SRT1720, the claim that this compound is a SIRT1 activator has been questioned[4][5][6] and further defended.[7][8]

Although SRT1720 is not currently undergoing clinical development, a related compound, SRT2104, is currently in clinical development for metabolic diseases.[9]

gollark: It is also possible to DIY gene therapy now, although that bit is probably not safe.
gollark: Apparently someone was naturally born with that, and didn't even horribly die, so it's probably safe to do.
gollark: I guess it would be nontrivial to do that in adults.
gollark: Can't you just remove the genes for myostatin?
gollark: https://media.discordapp.net/attachments/412764872816852994/899001509113626684/unknown.png

See also

References
  1. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, et al. (November 2007). "Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes". Nature. 450 (7170): 712–6. Bibcode:2007Natur.450..712M. doi:10.1038/nature06261. PMC 2753457. PMID 18046409.
  2. Minor RK, Baur JA, Gomes AP, Ward TM, Csiszar A, Mercken EM, et al. (Aug 2011). "SRT1720 improves survival and healthspan of obese mice". Scientific Reports. 1 (70): 70. Bibcode:2011NatSR...1E..70M. doi:10.1038/srep00070. PMC 3216557. PMID 22355589.
  3. Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G, et al. (March 2014). "The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet". Cell Reports. 6 (5): 836–43. doi:10.1016/j.celrep.2014.01.031. PMC 4010117. PMID 24582957.
  4. Pacholec M, Bleasdale JE, Chrunyk B, Cunningham D, Flynn D, Garofalo RS, et al. (March 2010). "SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1". The Journal of Biological Chemistry. 285 (11): 8340–51. doi:10.1074/jbc.M109.088682. PMC 2832984. PMID 20061378.
  5. Beher D, Wu J, Cumine S, Kim KW, Lu SC, Atangan L, Wang M (December 2009). "Resveratrol is not a direct activator of SIRT1 enzyme activity". Chemical Biology & Drug Design. 74 (6): 619–24. doi:10.1111/j.1747-0285.2009.00901.x. PMID 19843076.
  6. Zarse K, Schmeisser S, Birringer M, Falk E, Schmoll D, Ristow M (November 2010). "Differential effects of resveratrol and SRT1720 on lifespan of adult Caenorhabditis elegans". Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme. 42 (12): 837–9. doi:10.1055/s-0030-1265225. PMID 20925017.
  7. Callaway E (2010-08-16). "GlaxoSmithKline strikes back over anti-ageing pills: Drugs do work as thought, says pharmaceutical giant". Nature. doi:10.1038/news.2010.412.
  8. Dai H, Kustigian L, Carney D, Case A, Considine T, Hubbard BP, et al. (October 2010). "SIRT1 activation by small molecules: kinetic and biophysical evidence for direct interaction of enzyme and activator". The Journal of Biological Chemistry. 285 (43): 32695–703. doi:10.1074/jbc.M110.133892. PMC 2963390. PMID 20702418.
  9. "Sirtuin Pipeline". Sirtris Pharmaceuticals.
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