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, reached Phase II human trials for metabolic diseases.[9]
^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. PMC2753457. PMID 18046409.
^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. PMC3216557. PMID 22355589.
^ abMitchell 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. PMC4010117. PMID 24582957.
^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. PMC2832984. PMID 20061378.
^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. S2CID 205913187.
^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. 42 (12): 837–9. doi:10.1055/s-0030-1265225. PMID 20925017.
^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.
^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. PMC2963390. PMID 20702418.
^Thevis M, Schänzer W (March 2016). "Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis - Potential implications for sports drug testing programs". Rapid Communications in Mass Spectrometry. 30 (5): 635–51. Bibcode:2016RCMS...30..635T. doi:10.1002/rcm.7470. PMID 26842585. S2CID 206444739.
1720, experimental, drug, that, studied, sirtris, pharmaceuticals, intended, small, molecule, activator, sirtuin, subtype, sirt1, compound, been, studied, animals, safety, efficacy, humans, have, been, established, identifiersiupac, name, piperazin, ylmethyl, . SRT 1720 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 SRT 1720IdentifiersIUPAC name N 2 3 piperazin 1 ylmethyl imidazo 2 1 b 1 3 thiazol 6 yl phenyl quinoxaline 2 carboxamideCAS Number925434 55 5 YPubChem CID24180125IUPHAR BPS7703ChemSpider20581461UNIIDX3FHY76FZCompTox Dashboard EPA DTXSID00636045Chemical and physical dataFormulaC 25H 23N 7O SMolar mass469 57 g mol 13D model JSmol Interactive imageSMILES C6CNCCN6Cc n1c5 csc1nc5 c3ccccc3NC O c4cnc2ccccc2n4InChI InChI 1S C25H23N7OS c33 24 22 13 27 20 7 3 4 8 21 20 28 22 29 19 6 2 1 5 18 19 23 15 32 17 16 34 25 32 30 23 14 31 11 9 26 10 12 31 h1 8 13 15 16 26H 9 12 14H2 H 29 33 Key IASPBORHOMBZMY UHFFFAOYSA N verify Animal research EditIn 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 reached Phase II human trials for metabolic diseases 9 See also EditSRT 647 10 SRT 1460 SRT 2183 STAC 9References Edit 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 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 a b 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 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 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 amp Drug Design 74 6 619 24 doi 10 1111 j 1747 0285 2009 00901 x PMID 19843076 S2CID 205913187 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 42 12 837 9 doi 10 1055 s 0030 1265225 PMID 20925017 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 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 Sirtuin Pipeline Sirtris Pharmaceuticals Thevis M Schanzer W March 2016 Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis Potential implications for sports drug testing programs Rapid Communications in Mass Spectrometry 30 5 635 51 Bibcode 2016RCMS 30 635T doi 10 1002 rcm 7470 PMID 26842585 S2CID 206444739 This drug article relating to the gastrointestinal system is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title SRT 1720 amp oldid 1166943036, wikipedia, wiki, book, books, library,
