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Scientific Publications

Sirtris’ drugs candidates modulate the sirtuins, a recently discovered class of enzymes involved in the aging process.

At Sirtris, we have published numerous articles related to our scientific research. The following is a selection of our scientific publications.

+2011

Minor, RK, Baur, JA, Gomes, AP, Ward, TM, Csiszar, A, Mercken, EM, Abdelmohsen, K, Shin, Y-K, Canto, C, Scheibye-Knudsen, M, Krawczyk, M, Irusta, PM, Martin-Montalvo, A, Hubbard, BP, Zhang, Y, Lehrmann, E, While, AA, Price, NL, Swundell, WR, Pearson, KJ, Becker, KG, Bohr, VA, Gorospe, M, Egan, JM, Talan, MI, Auwerx, J, Westphal, CW, Ellis, JL, Ungvari, Z, Vlasuk, GP, Elliott, PJ, Sinclair, DA and de Cabo, R. SRT1720 improves survival and healthspan of obese mice. Sci. Rep. 2011; 1, 70; DOI:10.1038/srep00070
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JBCSzczepankiewicz, BG, Koppetsch, KJ, and Perni, RB. One-Step, Nonenzymatic Synthesis of O-Acetyl-ADP-ribose and Analogues from NAD and Carboxylates. J. Org. Chem. 2011; 76; 6465-6474
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Guarani V, Deflorian G, Franco CA, Krüger M, Phng LK, Bentley K, Toussaint L, Dequiedt F, Mostoslavsky R, Schmidt MH, Zimmermann B, Brandes RP, Mione M, Westphal CH, Braun T, Zeiher AM, Gerhardt H, Dimmeler S, Potente M. Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature 2011; 473: 234-238
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Blum CA, Ellis JL, Loh C, Ng PY, Perni RB, Stein RL. SIRT1 modulation as a novel approach to the treatment of diseases of aging. J Med Chem. 2011 Jan 27;54(2):417-32
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Breitenstein A, Stein S, Holy EW, Camici GG, Lohmann C, Akhmedov A, Spescha R, Elliott PJ, Westphal CH, Matter CM, Lüscher TF, Tanner FC. Sirt1 inhibition promotes in vivo arterial thrombosis and tissue factor expression in stimulated cells. Cardiovasc Res. 2011 Feb 1;89(2):464-72
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Robers MB, Loh C, Carlson CB, Yang H, Frey EA, Hermanson SB, Bi K. Measurement of the cellular deacetylase activity of SIRT1 on p53 via LanthaScreen® technology. Mol Biosyst. 2011;7(1):59-66
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+2010

Rutanen J, Yaluri N, Modi S, Pihlajamäki J, Vänttinen M, Itkonen P, Kainulainen S, Yamamoto H, Lagouge M, Sinclair DA, Elliott P, Westphal C, Auwerx J, Laakso M. SIRT1 mRNA expression may be associated with energy expenditure and insulin sensitivity. Diabetes. 2010 Apr;59(4):829-35
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Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, Boss O, Hirsch ML, Ribich S, Smith JJ, Israelian K, Westphal CH, Rodgers JT, Shioda T, Elson SL, Mulligan P, Najafi-Shoushtari H, Black JC, Thakur JK, Kadyk LC, Whetstine JR, Mostoslavsky R, Puigserver P, Li X, Dyson NJ, Hart AC, Näär AM. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010 Jul 1;24(13):1403-17
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Robers MB, Loh C, Carlson CB, Yang H, Frey EA, Hermanson SB, Bi K. Measurement of the cellular deacetylase activity of SIRT1 on p53 via LanthaScreen® technology. Mol. Biosyst. Epub 2010 Oct 8. PMID: 20931131
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JBCDai H, Kustigian L, Carney D, Case A., Considine T, Hubbard B, Perni R, Riera T, Szczepankiewicz B, Vlasuk G, Stein R. SIRT1 activation by small molecules - kinetic and biophysical evidence for direct interaction of enzyme and activator. J Biol Chem. 2010 Oct 22;285(43):32695-703
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Yoshizaki T, Schenk S, Imamura T, Babendure JL, Sonoda N, Bae EJ, Oh da Y, Lu M, Milne JC, Westphal C, Bandyopadhyay G, Olefsky JM. SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. Am J Physiol Endocrinol Metab. 2010; 298(3):E419-428
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+2009

Elliott PJ, Walpole S, Morelli L, Lambert PD, Lunsmann W, Westphal CH, Lavu S Resveratrol/SIRT-501. Drugs of the Future. 2009; 34(4): 291
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Vu CB, Milne JC, Carney DP, Song J, Choy W, Lambert PD, Gagne DJ, Hirsch M, Cote A, Davis M, Lainez E, Meade N, Normington K, Jirousek MR, Perni RB. Discovery of benzothiazole derivatives as efficacious and enterocyte-specific MTP inhibitors. Bioorg Med Chem Lett. 2009; 19(5):1416-1420
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Nakamaru Y, Vuppusetty C, Wada H, Milne JC, Ito M, Rossios C, Elliot M, Hogg J, Kharitonov S, Goto H, Bemis JE, Elliott P, Barnes PJ, Ito K. A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. FASEB J. 2009; 23(9):2810-2819
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Jin L, Wei W, Jiang Y, Peng H, Cai J, Mao C, Dai H, Choy W, Bemis JE, Jirousek MR, Milne JC, Westphal CH, Perni RB. Crystal structures of human SIRT3 displaying substrate-induced conformational changes. J Biol Chem. 2009; 284: 24394-24405
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Bemis JE, Vu CB, Xie R, Nunes JJ, Ng PY, Disch JS, Milne JC, Carney DP, Lynch AV, Jin L, Smith JJ, Lavu S, Iffland A, Jirousek MR, Perni RB. Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators. Bioorg Med Chem Lett. 2009 April 15; 19:2350-2353
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Smith JJ, Kenney RD, Gagne DJ, Frushour BP, Ladd W, Galonek HL, Israelian K, Song J, Razvadauskaite G, Lynch AV, Carney DP, Johnson RJ, Lavu S, Iffland A, Elliott PJ, Lambert PD, Elliston KO, Jirousek MR, Milne JC, Boss O. Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo. BMC Syst Biol. 2009 3:31
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Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J. AMPK regulates energy expenditure by modulating NAD(+) metabolism and SIRT1 activity. Nature. 2009; 458: 1056-1060
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Yoshizaki T, Milne JC, Imamura T, Schenk S, Sonoda N, Babendure JL, Lu JC, Smith JJ, Jirousek MR, Olefsky JM. SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. Mol Cell Biol, 2009 Mar; 29:1363-1374
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Vu CB, Bemis JE, Disch JS, Ng PY, Nunes JJ, Milne JC, Carney DP, Lynch AV, Smith JJ, Lavu S, Lambert PD, Gagne DJ, Jirousek MR, Schenk S, Olefsky JM, Perni RB. Discovery of Imidazo[1,2-b]thiazole Derivatives as Novel SIRT1 Activators. J Med Chem. 2009 Feb; 52(5):1275-1283
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Jin L, Galonek H, Israelian K, Choy W, Morrison M, Xia Y, Wang X, Xu Y, Yang Y, Smith JJ, Hoffmann E, Carney DP, Perni RB, Jirousek MR, Bemis JE, Milne JC, Sinclair DA, Westphal CH. Biochemical characterization, localization, and tissue distribution of the longer form of mouse SIRT3. Protein Sci. 2009 18(3):514-525
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+2008

Oberdoerffer P, Michan S, McVay M, Mostoslavsky R, Vann J, Park SK, Hartlerode A, Stegmuller J, Hafner A, Loerch P, Wright SM, Mills KD, Bonni A, Yankner BA, Scully R, Prolla TA, Alt FW, Sinclair DA. SIRT1 Redistribution on Chromatin Promotes Genome Stability but Alters Gene Expression during Aging. Cell. 2008 135(5): 907-18
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Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, Milne JC, Lambert PD, Mataki C, Elliott PJ, Auwerx J. Specific SIRT1 Activation Mimics Low Energy Levels and Protects against Diet-Induced Metabolic Disorders by Enhancing Fat Oxidation. Cell Metabolism. 2008 8(5): 347-58
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Szczepankiewicz BG, Ng PY. Sirtuin modulators: targets for metabolic diseases and beyond. Curr Top Med Chem. 2008 8(17):1533-1544
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Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates III J, Olefsky J, Guarente L, Montminy M. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature. 2008 456: 269-73
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Lavu S, Boss O, Elliott PJ, Lambert PD. Sirtuins — novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov. 2008 7(10): 841-53
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Pearson KJ, Baur JA, Lewis KN, Peskin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R. Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. Cell Metabolism. 2008 8(2): 157-68
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Elliott PJ, Jirousek M. Sirtuins: Novel targets for metabolic disease. Current Opinion in Investigational Drugs. 2008 9:371-378
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Milne JC, Denu JM. The Sirtuin family: therapeutic targets to treat diseases of aging. Curr Opin Chem Biol. 2008 12(1):11-7
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+2007

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. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007 Nov 29; 450(7170):712-6. PMID: 18046409
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Westphal CH, Dipp MA, Guarente L. A therapeutic role for sirtuins in diseases of aging? Trends Biochem Sci. 2007 32(12):555-60
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Shindler KS, Ventura E, Rex TS, Elliott P, Rostami A. SIRT1 activation confers neuroprotection in experimental optic neuritis. Invest Ophthalmol Vis Sci. 2007 48(8):3602-9
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+2006

Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 127(6):1109-22
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Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 444(7117):337-42
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