Two novel SIRT1 activators, SCIC2 and SCIC2.1, enhance SIRT1-mediated effects in stress response and senescence

References

• Imai S, Armstrong CM, Kaeberlein M, et al. Transcriptional silencing and longevity protein SIR2 is an NAD-dependent histone deacetylase. Nature. 2000 Feb 17;403(6771):795–800.
   PubMed Web of Science ®Google Scholar
• Klar AJ, Fogel S, Radin DN. Switching of a mating-type a mutant allele in budding yeast Saccharomyces cerevisiae. Genetics. 1979 Jul;92(3):759–776.
   PubMed Web of Science ®Google Scholar
• Ivy JM, Klar AJ, Hicks JB. Cloning and characterization of four SIR genes of Saccharomyces cerevisiae. Mol Cell Biol. 1986 Feb;6(2):688–702.
   PubMed Web of Science ®Google Scholar
• Rine J, Herskowitz I. Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics. 1987 May;116(1):9–22.
   PubMed Web of Science ®Google Scholar
• Brachmann CB, Sherman JM, Devine SE, et al. The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability. Genes Dev. 1995 Dec 1;9(23):2888–2902.
   PubMed Web of Science ®Google Scholar
• Derbyshire MK, Weinstock KG, Strathern JN. HST1, a new member of the SIR2 family of genes. Yeast. 1996 Jun 15;12(7):631–640.
   PubMed Web of Science ®Google Scholar
• Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology. 2017 Aug;18(4):447–476.
   PubMed Web of Science ®Google Scholar
• Michan S, Sinclair D. Sirtuins in mammals: insights into their biological function. Biochem J. 2007 May 15;404(1):1–13.
   PubMed Web of Science ®Google Scholar
• Sauve AA. Sirtuins. Biochim Biophys Acta. 2010 Aug;1804(8):1565–1566.
   PubMedGoogle Scholar
• Kupis W, Palyga J, Tomal E, et al. The role of sirtuins in cellular homeostasis. J Physiol Biochem. 2016 Sep;72(3):371–380.
   PubMed Web of Science ®Google Scholar
• Cohen HY, Miller C, Bitterman KJ, et al. Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science. 2004 Jul 16;305(5682):390–392.
   PubMed Web of Science ®Google Scholar
• Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD(+) and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 2016 Nov;17(11):679–690.
   PubMed Web of Science ®Google Scholar
• Wang Y, He J, Liao M, et al. An overview of sirtuins as potential therapeutic target: structure, function and modulators. Eur J Med Chem. 2019 Jan 1;161:48–77.
   PubMed Web of Science ®Google Scholar
• Dai H, Sinclair DA, Ellis JL, et al. Sirtuin activators and inhibitors: promises, achievements, and challenges. Pharmacol Ther. 2018;188:140–154.
   PubMed Web of Science ®Google Scholar
• Morris BJ. Seven sirtuins for seven deadly diseases of aging. Free Radic Biol Med. 2013 Mar;56:133–171.
   PubMed Web of Science ®Google Scholar
• Bordone L, Cohen D, Robinson A, et al. SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell. 2007 Dec;6(6):759–767.
   PubMed Web of Science ®Google Scholar
• Hubbard BP, Sinclair DA. Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci. 2014 Mar;35(3):146–154.
   PubMed Web of Science ®Google Scholar
• Schiedel M, Robaa D, Rumpf T, et al. The current state of NAD(+) -dependent histone deacetylases (Sirtuins) as novel therapeutic targets. Med Res Rev. 2018 Jan;38(1):147–200.
   PubMed Web of Science ®Google Scholar
• Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006 Jun;5(6):493–506.
   PubMed Web of Science ®Google Scholar
• Rascon B, Hubbard BP, Sinclair DA, et al. The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. Aging (Albany NY). 2012 Jul;4(7):499–508.
   PubMedGoogle Scholar
• Berman AY, Motechin RA, Wiesenfeld MY, et al. The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol. 2017;1:1–9.
   PubMed Web of Science ®Google Scholar
• Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J Biol Chem. 2005 Apr 29;280(17):17187–17195.
   PubMed Web of Science ®Google Scholar
• Dyck GJB, Raj P, Zieroth S, et al. The effects of resveratrol in patients with cardiovascular disease and heart failure: a narrative review. Int J Mol Sci. 2019 Feb 19;20(4):904.
   PubMed Web of Science ®Google Scholar
• Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006 Dec 15;127(6):1109–1122.
   PubMed Web of Science ®Google Scholar
• Carafa V, Rotili D, Forgione M, et al. Sirtuin functions and modulation: from chemistry to the clinic. Clin Epigenetics. 2016;8:61.
   PubMed Web of Science ®Google Scholar
• Valente S, Mellini P, Spallotta F, et al. 1,4-dihydropyridines active on the SIRT1/AMPK pathway ameliorate skin repair and mitochondrial function and exhibit inhibition of proliferation in cancer cells. J Med Chem. 2016 Feb 25;59(4):1471–1491.
   PubMed Web of Science ®Google Scholar
• Hubbard BP, Gomes AP, Dai H, et al. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science. 2013 Mar 8;339(6124):1216–1219.
   PubMed Web of Science ®Google Scholar
• Sinclair DA, Guarente L. Small-molecule allosteric activators of sirtuins. Annu Rev Pharmacol Toxicol. 2014;54:363–380.
   PubMed Web of Science ®Google Scholar
• Vu CB, Bemis JE, Disch JS, et al. Discovery of imidazo[1,2-b]thiazole derivatives as novel SIRT1 activators. J Med Chem. 2009 Mar 12;52(5):1275–1283.
   PubMed Web of Science ®Google Scholar
• Pacholec M, Bleasdale JE, Chrunyk B, et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem. 2010 Mar 12;285(11):8340–8351.
   PubMed Web of Science ®Google Scholar
• Ren Y, Du C, Shi Y, et al. The SIRT1 activator, SRT1720, attenuates renal fibrosis by inhibiting CTGF and oxidative stress. Int J Mol Med. 2017 May;39(5):1317–1324.
   PubMed Web of Science ®Google Scholar
• Bemis JE, Vu CB, Xie R, et al. Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators. Bioorg Med Chem Lett. 2009 Apr 15;19(8):2350–2353.
   PubMed Web of Science ®Google Scholar
• van der Meer AJ, Scicluna BP, Moerland PD, et al. The selective sirtuin 1 activator SRT2104 reduces endotoxin-induced cytokine release and coagulation activation in humans. Crit Care Med. 2015 Jun;43(6):e199–202.
   PubMed Web of Science ®Google Scholar
• Jiao D, Zhang H, Jiang Z, et al. MicroRNA-34a targets sirtuin 1 and leads to diabetes-induced testicular apoptotic cell death. J Mol Med. 2018 Sep;96(9):939–949.
   PubMed Web of Science ®Google Scholar
• Wu H, Wu J, Zhou S, et al. SRT2104 attenuates diabetes-induced aortic endothelial dysfunction via inhibition of P53. J Endocrinol. 2018 Apr;237(1):1–14.
   PubMed Web of Science ®Google Scholar
• Nayagam VM, Wang X, Tan YC, et al. SIRT1 modulating compounds from high-throughput screening as anti-inflammatory and insulin-sensitizing agents. J Biomol Screen. 2006 Dec;11(8):959–967.
   PubMedGoogle Scholar
• Hoffmann E, Wald J, Lavu S, et al. Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man. Br J Clin Pharmacol. 2013 Jan;75(1):186–196.
   PubMed Web of Science ®Google Scholar
• Ma F, Wu J, Jiang Z, et al. P53/NRF2 mediates SIRT1’s protective effect on diabetic nephropathy. Biochim Biophys Acta Mol Cell Res. 2019 Aug;1866(8):1272–1281.
   PubMed Web of Science ®Google Scholar
• Napper AD, Hixon J, McDonagh T, et al. Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. J Med Chem. 2005 Dec 15;48(25):8045–8054.
   PubMed Web of Science ®Google Scholar
• Smith MR, Syed A, Lukacsovich T, et al. A potent and selective sirtuin 1 inhibitor alleviates pathology in multiple animal and cell models of Huntington’s disease. Hum Mol Genet. 2014 Jun 1;23(11):2995–3007.
   PubMed Web of Science ®Google Scholar
• Sussmuth SD, Haider S, Landwehrmeyer GB, et al. An exploratory double-blind, randomized clinical trial with selisistat, a SIRT1 inhibitor, in patients with Huntington’s disease. Br J Clin Pharmacol. 2015 Mar;79(3):465–476.
   PubMed Web of Science ®Google Scholar
• Zhou Z, Ma T, Zhu Q, et al. Recent advances in inhibitors of sirtuin1/2: an update and perspective. Future Med Chem. 2018 Apr 1;10(8):907–934.
   PubMed Web of Science ®Google Scholar
• Nunez S, Venhorst J, Kruse CG. Target-drug interactions: first principles and their application to drug discovery. Drug Discov Today. 2012 Jan;17(1–2):10–22.
   PubMed Web of Science ®Google Scholar
• Zhao X, Allison D, Condon B, et al. The 2.5 A crystal structure of the SIRT1 catalytic domain bound to nicotinamide adenine dinucleotide (NAD+) and an indole (EX527 analogue) reveals a novel mechanism of histone deacetylase inhibition. J Med Chem. 2013 Feb 14;56(3):963–969.
   PubMed Web of Science ®Google Scholar
• Dai H, Case AW, Riera TV, et al. Crystallographic structure of a small molecule SIRT1 activator-enzyme complex. Nat Commun. 2015 Jul 2;6:7645.
   PubMed Web of Science ®Google Scholar
• Cao D, Wang M, Qiu X, et al. Structural basis for allosteric, substrate-dependent stimulation of SIRT1 activity by resveratrol. Genes Dev. 2015 Jun 15;29(12):1316–1325.
   PubMed Web of Science ®Google Scholar
• Borges F, Roleira F, Milhazes N, et al. Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and biological activity. Curr Med Chem. 2005;12(8):887–916.
   PubMed Web of Science ®Google Scholar
• Bajusz D, Racz A, Heberger K. Why is Tanimoto index an appropriate choice for fingerprint-based similarity calculations? J Cheminform. 2015;7:20.
   PubMed Web of Science ®Google Scholar
• Hidalgo IJ, Raub TJ, Borchardt RT. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology. 1989 Mar;96(3):736–749.
   PubMed Web of Science ®Google Scholar
• Artursson P. Epithelial transport of drugs in cell culture. I: a model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. J Pharm Sci. 1990 Jun;79(6):476–482.
   PubMed Web of Science ®Google Scholar
• Mansfeld FM, Synthesis IT. Plasma stability of disulfide-bridged cyclic endomorphin-1 derivatives. Int J Org Chem. 2012 Mar;2(1):1–6.
   Google Scholar
• Ghosh S, Zhou Z. SIRTain regulators of premature senescence and accelerated aging. Protein Cell. 2015 May;6(5):322–333.
   PubMed Web of Science ®Google Scholar
• Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999 Oct 1;13(19):2570–2580.
   PubMed Web of Science ®Google Scholar
• Rogina B, Helfand SL. SIR2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA. 2004 Nov 9;101(45):15998–16003.
   PubMed Web of Science ®Google Scholar
• Kumar A, Chauhan S. How much successful are the medicinal chemists in modulation of SIRT1: a critical review. Eur J Med Chem. 2016 Aug 25;119:45–69.
   PubMed Web of Science ®Google Scholar
• McBurney MW, Clark-Knowles KV, Caron AZ, et al. SIRT1 is a highly networked protein that mediates the adaptation to chronic physiological stress. Genes Cancer. 2013 Mar;4(3–4):125–134.
   PubMedGoogle Scholar
• Luo J, Nikolaev AY, Imai S, et al. Negative control of p53 by SIR2alpha promotes cell survival under stress. Cell. 2001 Oct 19;107(2):137–148.
   PubMed Web of Science ®Google Scholar
• Wang RH, Sengupta K, Li C, et al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell. 2008 Oct 7;14(4):312–323.
   PubMed Web of Science ®Google Scholar
• Gan L, Mucke L. Paths of convergence: sirtuins in aging and neurodegeneration. Neuron. 2008 Apr 10;58(1):10–14.
   PubMed Web of Science ®Google Scholar
• Potente M, Ghaeni L, Baldessari D, et al. SIRT1 controls endothelial angiogenic functions during vascular growth. Genes Dev. 2007 Oct 15;21(20):2644–2658.
   PubMed Web of Science ®Google Scholar
• Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab. 2014 Mar;25(3):138–145.
   PubMed Web of Science ®Google Scholar
• Milite C, Feoli A, Horton JR, et al. Discovery of a novel chemotype of histone lysine methyltransferase EHMT1/2 (GLP/G9a) inhibitors: rational design, synthesis, biological evaluation, and co-crystal structure. J Med Chem. 2019 Mar 14;62(5):2666–2689.
   PubMed Web of Science ®Google Scholar
• Morris GM, Huey R, Lindstrom W, et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem. 2009 Dec;30(16):2785–2791.
   PubMed Web of Science ®Google Scholar