SRT1720

SRT1720
Systematic (IUPAC) name
N-[2-[3-(piperazin-1-ylmethyl)imidazo[2,1-b][1,3]thiazol-6-yl]phenyl]quinoxaline-2-carboxamide
Clinical data
Pregnancy cat.  ?
Legal status  ?
Identifiers
ATC code  ?
PubChem CID 24180125
Chemical data
Formula C25H23N7OS 
Mol. mass 469.560 g/mol
SMILES eMolecules & PubChem
 Y(what is this?)  (verify)

SRT1720 is a drug developed by Sirtris Pharmaceuticals intended as a small-molecule activator of the sirtuin subtype SIRT1. It has similar activity in the body to the known SIRT1 activator resveratrol, but is 1000x more potent. In animal studies it was found to improve insulin sensitivity and lower plasma glucose levels in fat, muscle and liver tissue, and increased mitochondrial and metabolic function.[1] A study of SRT1720 conducted by the National Institute on Aging found that the drug may extend the lifespan of obese mice by 44%[2] . Although SRT1720 is not currently undergoing clinical development, a related compound, SRT2104, is currently in clinical development for metabolic diseases.[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]

See also

References

  1. ^ Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH (November 2007). "Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes". Nature 450 (7170): 712–6. doi:10.1038/nature06261. PMC 2753457. PMID 18046409. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2753457. 
  2. ^ Nicholas, Wade (18 August 2011). "Drug Is Found to Extend Lives of Obese Mice". The New York Times. http://www.nytimes.com/2011/08/19/science/19fat.html. Retrieved 18 August 2011. 
  3. ^ "Sirtuin Pipeline". Sirtris Pharmaceuticals. http://www.sirtrispharma.com/pipeline.html. 
  4. ^ Pacholec M, Chrunyk BA, Cunningham D, Flynn D, Griffith DA, Griffor M, Loulakis P, Pabst B, Qiu X, Stockman B, Thanabal V, Varghese A, Ward J, Withka J, Ahn K (January 2010). "SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1". J Biol Chem 285 (11): 8340–8351. doi:10.1074/jbc.M109.088682. PMC 2832984. PMID 20061378. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2832984. 
  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". Chem Biol Drug Des 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. (2010). "Differential Effects of Resveratrol and SRT1720 on Lifespan of AdultCaenorhabditis elegans". Hormone and Metabolic Research 42 (12): 837–839. doi:10.1055/s-0030-1265225. PMID 20925017.  edit
  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. http://www.nature.com/news/2010/100816/full/news.2010.412.html. 
  8. ^ Dai H, Kustigian L, Carney D, Case A, Considine T, Hubbard BP, Perni RB, Riera TV, Szczepankiewicz B, Vlasuk GP, Stein RL (August 2010). "SIRT1 activation by small molecules - kinetic and biophysical evidence for direct interaction of enzyme and activator". J Biol Chem 285 (43): 32695–32703. doi:10.1074/jbc.M110.133892. PMC 2963390. PMID 20702418. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2963390.