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
Identifiers
PubChem CID 24180125
IUPHAR/BPS 7703
Chemical data
Formula C25H23N7OS
Molar mass 469.560 g/mol
  (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): 70. doi:10.1038/srep00070. PMC 3216557. 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): 836–43. doi:10.1016/j.celrep.2014.01.031. PMID 24582957. 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. 
  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.