SRT1720

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

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.

Animal research[edit]

In animal models of obesity and diabetes 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] 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]

See also[edit]

References[edit]

  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. 
  2. ^ Minor RK; Baur JA; Gomes AP; Ward TM; Csiszar A; Mercken EM; Abdelmohsen K; Shin YK; Canto C; Scheibye-Knudsen M; Krawczyk M; Irusta PM; Martín-Montalvo A; Hubbard BP; Zhang Y; Lehrmann E; White AA; Price NL; Swindell WR; Pearson KJ; Becker KG; Bohr VA; Gorospe M; Egan JM; Talan MI; Auwerx J; Westphal CH; Ellis JL; Ungvari Z; Vlasuk GP; Elliott PJ; Sinclair DA; de Cabo R (Aug 2011). "SRT1720 improves survival and healthspan of obese mice". Scientific Reports 1 (70). doi:10.1038/srep00070. PMID 22355589. Retrieved 1 March 2014. 
  3. ^ a b Mitchell SJ, Martin-Montalvo A, Mercken EM, et al (Feb 2014). "The SIRT1 Activator SRT1720 Extends Lifespan and Improves Health of Mice Fed a Standard Diet". Cell Reports 6 (4). doi:10.1016/j.celrep.2014.01.031. Retrieved 1 March 2014. 
  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. 
  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. 
  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. 
  9. ^ "Sirtuin Pipeline". Sirtris Pharmaceuticals.