Sirtuin Inhibitors as Anticancer Agents

References

• Lin SJ , DefossezPA, GuarenteL. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science289 (5487), 2126–2128 (2000).
   PubMed Web of Science ®Google Scholar
• Imai SI , ArmstrongCM, KaeberleinM, GuarenteL. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature403 (6771), 795–800 (2000).
   PubMed Web of Science ®Google Scholar
• Haigis MC , SinclairDA. Mammalian sirtuins: biological insights and disease relevance. Annu. Rev. Pathol.5 (1), 253–295 (2010).
   PubMedGoogle Scholar
• Morris BJ . Seven sirtuins for seven deadly diseases of aging. Free Radic. Biol. Med.56 (0), 133–171 (2013).
   PubMedGoogle Scholar
• Roth M , ChenWY. Sorting out functions of sirtuins in cancer. Oncogene doi:10.1038/onc.2013.120 (2013) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Lin Z , FangD. The roles of SIRT1 in cancer. Genes Cancer4 (3–4), 97–104 (2013).
   PubMedGoogle Scholar
• Song NY , SurhYJ. Janus-faced role of SIRT1 in tumorigenesis. Ann. NY Acad. Sci.1271, 10–19 (2012).
   PubMed Web of Science ®Google Scholar
• Firestein R , BlanderG, MichanSet al. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE3 (4), e2020 (2008).
   PubMed Web of Science ®Google Scholar
• Herranz D , Munoz-MartinM, CanameroMet al. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat. Commun.1, 3 (2010).
   PubMedGoogle Scholar
• Wang RH , SenguptaK, LiCet al. Impaired DNA damage response, genome instability, and tumorigenesis in SIRT1 mutant mice. Cancer Cell14 (4), 312–323 (2008).
   PubMed Web of Science ®Google Scholar
• Yeung F , HobergJE, RamseyCSet al. Modulation of NF-êB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J.23, 2369–2380 (2004).
   PubMed Web of Science ®Google Scholar
• Lim J-H , LeeY-M, ChunY-S, ChenJ, KimJ-E, ParkJ-W. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1α. Mol. Cell38 (6), 864–878 (2010).
   PubMed Web of Science ®Google Scholar
• Wang R-H , ZhengY, KimH-Set al. Interplay among BRCA1, SIRT1, and survivin during BRCA1-associated tumorigenesis. Mol. Cell32 (1), 11–20 (2008).
   PubMed Web of Science ®Google Scholar
• Herranz D , MaraverA, CanameroMet al. SIRT1 promotes thyroid carcinogenesis driven by PTEN deficiency. Oncogene32 (34), 4052–4056 (2013).
   PubMed Web of Science ®Google Scholar
• Yuan H , WangZ, LiLet al. Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis. Blood119 (8), 1904–1914 (2012).
   PubMed Web of Science ®Google Scholar
• Leko V , ParkGJ, LaoU, SimonJA, BedalovA. Enterocyte-specific inactivation of SIRT1 reduces tumor load in the APC(+/min) mouse model. PLoS ONE8 (6), e66283 (2013).
   PubMed Web of Science ®Google Scholar
• Chen L . Medicinal chemistry of sirtuin inhibitors. Curr. Med. Chem.18 (13), 1936–1946 (2011).
   PubMed Web of Science ®Google Scholar
• Wang Z , YuanH, RothM, StarkJM, BhatiaR, ChenWY. SIRT1 deacetylase promotes acquisition of genetic mutations for drug resistance in CML cells. Oncogene32 (5), 589–598 (2013).
   PubMed Web of Science ®Google Scholar
• Luo J , NikolaevAY, ImaiSIet al. Negative control of p53 by Sir2a promotes cell survival under stress. Cell107 (2), 137–148 (2001).
   PubMed Web of Science ®Google Scholar
• Yang Y , HouH, HallerEM, NicosiaSV, BaiW. Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation. EMBO J.24 (5), 1021–1032 (2005).
   PubMed Web of Science ®Google Scholar
• Wang F , ChanCH, ChenK, GuanX, LinHK, TongQ. Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene31 (12), 1546–1557 (2012).
   PubMed Web of Science ®Google Scholar
• Daitoku H , HattaM, MatsuzakiHet al. Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proc. Natl Acad. Sci. USA101 (27), 10042–10047 (2004).
   PubMed Web of Science ®Google Scholar
• Choi HK , ChoKB, PhuongNTet al. SIRT1-mediated FoxO1 deacetylation is essential for multidrug resistance-associated protein 2 expression in tamoxifen-resistant breast cancer cells. Mol. Pharm.10 (7), 2517–2527 (2013).
   PubMedGoogle Scholar
• Menssen A , HydbringP, KapelleKet al. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc. Natl Acad. Sci. USA109 (4), E187–E196 (2012).
   PubMed Web of Science ®Google Scholar
• Marshall GM , LiuPY, GherardiSet al. SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability. PLoS Genet.7 (6), e1002135 (2011).
   PubMed Web of Science ®Google Scholar
• Yuan J , Minter-DykhouseK, LouZ. A c-Myc–SIRT1 feedback loop regulates cell growth and transformation. J. Cell Biol.185 (2), 203–211 (2009).
   PubMed Web of Science ®Google Scholar
• Holloway KR , CalhounTN, SaxenaMet al. SIRT1 regulates Dishevelled proteins and promotes transient and constitutive Wnt signaling. Proc. Natl Acad. Sci. USA107 (20), 9216–9221 (2010).
   PubMed Web of Science ®Google Scholar
• Saxena M , DykesSS, MalyarchukS, WangAE, CardelliJA, PruittK. The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration. Oncogene doi:10.1038/onc.2013.549 (2013) ( Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Holloway KR , BarbieriA, MalyarchukSet al. SIRT1 positively regulates breast cancer associated human aromatase (CYP19A1) expression. Mol. Endocrinol.27 (3), 480–490 (2013).
   PubMedGoogle Scholar
• O'Hagan HM , WangW, SenSet al. Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. Cancer Cell20 (5), 606–619 (2011).
   PubMed Web of Science ®Google Scholar
• Bosch-Presegué L , Raurell-VilaH, Marazuela-DuqueAet al. Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection. Mol. Cell42 (2), 210–223 (2011).
   PubMed Web of Science ®Google Scholar
• Murayama A , OhmoriK, FujimuraAet al. Epigenetic control of rDNA loci in response to intracellular energy status. Cell133 (4), 627–639 (2008).
   PubMed Web of Science ®Google Scholar
• Chen WY , WangDH, YenRC, LuoJ, GuW, BaylinSB. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell123 (3), 437–448 (2005).
   PubMed Web of Science ®Google Scholar
• Nemoto S , FergussonMM, FinkelT. Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science306 (5704), 2105–2108 (2004).
   PubMed Web of Science ®Google Scholar
• Gallardo E , NavarroA, VinolasNet al. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis30 (11), 1903–1909 (2009).
   PubMed Web of Science ®Google Scholar
• Yamakuchi M , FerlitoM, LowensteinCJ. miR-34a repression of SIRT1 regulates apoptosis. Proc. Natl Acad. Sci. USA105 (36), 13421–13426 (2008).
   PubMed Web of Science ®Google Scholar
• Kim H-S , VassilopoulosA, WangR-Het al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell20 (4), 487–499 (2011).
   PubMed Web of Science ®Google Scholar
• Serrano L , Martinez-RedondoP, Marazuela-DuqueAet al. The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation. Genes Dev.27 (6), 639–653 (2013).
   PubMed Web of Science ®Google Scholar
• Lin R , TaoR, GaoXet al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol. Cell51 (4), 506–518 (2013).
   PubMed Web of Science ®Google Scholar
• Heltweg B , GatbontonT, SchulerADet al. Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res.66 (8), 4368–4377 (2006).
   PubMed Web of Science ®Google Scholar
• Li Y , MatsumoriH, NakayamaYet al. SIRT2 down-regulation in HeLa can induce p53 accumulation via p38 MAPK activation-dependent p300 decrease, eventually leading to apoptosis. Genes Cells16 (1), 34–45 (2011).
   PubMed Web of Science ®Google Scholar
• Liu G , SuL, HaoXet al. Salermide up-regulates death receptor 5 expression through the ATF4-ATF3-CHOP axis and leads to apoptosis in human cancer cells. J. Cell. Mol. Med.16 (7), 1618–1628 (2012).
   PubMed Web of Science ®Google Scholar
• Liu PY , XuN, MalyukovaAet al. The histone deacetylase SIRT2 stabilizes Myc oncoproteins. Cell Death Differ.20 (3), 503–514 (2013).
   PubMed Web of Science ®Google Scholar
• Sunami Y , ArakiM, HironakaYet al. Inhibition of the NAD-dependent protein deacetylase SIRT2 induces granulocytic differentiation in human leukemia cells. PLoS ONE8 (2), e57633 (2013).
   PubMed Web of Science ®Google Scholar
• Chen J , ChanAW, ToKFet al. SIRT2 overexpression in hepatocellular carcinoma mediates epithelial to mesenchymal transition by protein kinase B/glycogen synthase kinase-3beta/beta-catenin signaling. Hepatology57 (6), 2287–2298 (2013).
   PubMed Web of Science ®Google Scholar
• He X , NieH, HongY, ShengC, XiaW, YingW. SIRT2 activity is required for the survival of C6 glioma cells. Biochem. Biophys. Res. Comm.417 (1), 468–472 (2012).
   PubMed Web of Science ®Google Scholar
• McCarthy AR , SachwehMC, HigginsMet al. Tenovin-D3, a novel small-molecule inhibitor of sirtuin SirT2, increases p21 (CDKN1A) expression in a p53-independent manner. Mol. Cancer. Ther.12 (4), 352–360 (2013).
   PubMed Web of Science ®Google Scholar
• Zhang Y , AuQ, ZhangM, BarberJR, NgSC, ZhangB. Identification of a small molecule SIRT2 inhibitor with selective tumor cytotoxicity. Biochem. Biophys. Res. Commun.386 (4), 729–733 (2009).
   PubMed Web of Science ®Google Scholar
• Yang MH , LaurentG, BauseASet al. HDAC6 and SIRT2 regulate the acetylation state and oncogenic activity of mutant K-RAS. Mol. Cancer Res.11 (9), 1072–1077 (2013).
   PubMed Web of Science ®Google Scholar
• Jing E , GestaS, KahnCR. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab.6 (2), 105–114 (2007).
   PubMed Web of Science ®Google Scholar
• Zhao Y , YangJ, LiaoWet al. Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. Nat. Cell Biol.12 (7), 665–675 (2010).
   PubMed Web of Science ®Google Scholar
• Ramakrishnan G , DavaakhuuG, KaplunLet al. Sirt2 deacetylase is a novel AKT binding partner critical for AKT activation by insulin. J. Biol. Chem.289 (9), 6054–6066 (2014).
   PubMed Web of Science ®Google Scholar
• Zhao D , ZouS-W, LiuYet al. Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell23 (4), 464–476 (2013).
   PubMed Web of Science ®Google Scholar
• Soung YH , PruittK, ChungJ. Epigenetic silencing of ARRDC3 expression in basal-like breast cancer cells. Sci. Rep.4, 3846 (2014).
   PubMed Web of Science ®Google Scholar
• Kim HS , PatelK, Muldoon-JacobsKet al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell17 (1), 41–52 (2010).
   PubMed Web of Science ®Google Scholar
• Finley LW , CarracedoA, LeeJet al. SIRT3 opposes reprogramming of cancer cell metabolism through HIF1alpha destabilization. Cancer Cell19 (3), 416–428 (2011).
   PubMed Web of Science ®Google Scholar
• Bell EL , EmerlingBM, RicoultSJ, GuarenteL. SirT3 suppresses hypoxia inducible factor 1alpha and tumor growth by inhibiting mitochondrial ROS production. Oncogene30 (26), 2986–2996 (2011).
   PubMed Web of Science ®Google Scholar
• Shulga N , Wilson-SmithR, PastorinoJG. Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria. J. Cell Sci.123 (Pt 6), 894–902 (2010).
   PubMed Web of Science ®Google Scholar
• Hafner AV , DaiJ, GomesAPet al. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY), 2 (12), 914–923 (2010).
   PubMedGoogle Scholar
• Sundaresan NR , GuptaM, KimG, RajamohanSB, IsbatanA, GuptaMP. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J. Clin. Invest.119 (9), 2758–2771 (2009).
   PubMed Web of Science ®Google Scholar
• Jacobs KM , PenningtonJD, BishtKSet al. SIRT3 interacts with the daf-16 homolog FOXO3a in the mitochondria, as well as increases FOXO3a dependent gene expression. Int. J. Biol. Sci.4 (5), 291–299 (2008).
   PubMed Web of Science ®Google Scholar
• Tseng AH , ShiehSS, WangDL. SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic. Biol. Med.63, 222–234 (2013).
   PubMed Web of Science ®Google Scholar
• Inuzuka H , GaoD, FinleyLWet al. Acetylation-dependent regulation of Skp2 function. Cell150 (1), 179–193 (2012).
   PubMed Web of Science ®Google Scholar
• Iwahara T , BonasioR, NarendraV, ReinbergD. SIRT3 functions in the nucleus in the control of stress-related gene expression. Mol. Cell. Biol.32 (24), 5022–5034 (2012).
   PubMed Web of Science ®Google Scholar
• Sundaresan NR , SamantSA, PillaiVB, RajamohanSB, GuptaMP. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol. Cell Biol.28 (20), 6384–6401 (2008).
   PubMed Web of Science ®Google Scholar
• Haigis MC , MostoslavskyR, HaigisKMet al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell126 (5), 941–954 (2006).
   PubMed Web of Science ®Google Scholar
• Csibi A , FendtSM, LiCet al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell153 (4), 840–854 (2013).
   PubMed Web of Science ®Google Scholar
• Jeong SM , XiaoC, FinleyLWet al. SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell23 (4), 450–463 (2013).
   PubMed Web of Science ®Google Scholar
• Yu J , SadhukhanS, NoriegaLGet al. Metabolic characterization of a Sirt5 deficient mouse model. Sci. Rep.3, 2806 (2013).
   PubMed Web of Science ®Google Scholar
• Nakagawa T , LombDJ, HaigisMC, GuarenteL. SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell137 (3), 560–570 (2009).
   PubMed Web of Science ®Google Scholar
• Du J , ZhouY, SuXet al. Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science334 (6057), 806–809 (2011).
   PubMed Web of Science ®Google Scholar
• Peng C , LuZ, XieZet al. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteomics10 (12), M111.012658 (2011).
   Web of Science ®Google Scholar
• Park J , ChenY, TishkoffDXet al. SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol. Cell50 (6), 919–930 (2013).
   PubMed Web of Science ®Google Scholar
• Michishita E , McCordRA, BerberEet al. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature452 (7186), 492–496 (2008).
   PubMed Web of Science ®Google Scholar
• Sebastian C , ZwaansBM, SilbermanDMet al. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell151 (6), 1185–1199 (2012).
   PubMed Web of Science ®Google Scholar
• Jiang H , KhanS, WangYet al. SIRT6 regulates TNF-alpha secretion through hydrolysis of long-chain fatty acyl lysine. Nature496 (7443), 110–113 (2013).
   PubMed Web of Science ®Google Scholar
• Gil R , BarthS, KanfiY, CohenHY. SIRT6 exhibits nucleosome-dependent deacetylase activity. Nucleic Acids Res.41 (18), 8537–8545 (2013).
   PubMed Web of Science ®Google Scholar
• Feldman JL , BaezaJ, DenuJM. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J. Biol. Chem.288 (43), 31350–31356 (2013).
   PubMed Web of Science ®Google Scholar
• Mostoslavsky R , ChuaKF, LombardDBet al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell124 (2), 315–329 (2006).
   PubMed Web of Science ®Google Scholar
• Chen S , SeilerJ, Santiago-ReicheltM, FelbelK, GrummtI, VoitR. Repression of RNA polymerase I upon stress is caused by inhibition of RNA-dependent deacetylation of PAF53 by SIRT7. Mol. Cell52 (3), 303–313 (2013).
   PubMed Web of Science ®Google Scholar
• Michishita E , ParkJY, BurneskisJM, BarrettJC, HorikawaI. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol. Biol. Cell16 (10), 4623–4635 (2005).
   PubMed Web of Science ®Google Scholar
• Ford E , VoitR, LisztG, MaginC, GrummtI, GuarenteL. Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes Dev.20 (9), 1075–1080 (2006).
   PubMed Web of Science ®Google Scholar
• Tsai YC , GrecoTM, CristeaIM. SIRT7 plays a role in ribosome biogenesis and protein synthesis. Mol. Cell. Proteomics13 (1), 73–83 (2013).
   PubMed Web of Science ®Google Scholar
• Barber MF , Michishita-KioiE, XiYet al. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature487 (7405), 114–118 (2012).
   PubMed Web of Science ®Google Scholar
• Shin J , HeM, LiuYet al. SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease. Cell Rep.5 (3), 654–665 (2013).
   PubMed Web of Science ®Google Scholar
• Hubbard BP , SinclairDA. Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol. Sci.35, 146–154 (2014).
   PubMed Web of Science ®Google Scholar
• Jackson MD , SchmidtMT, OppenheimerNJ, DenuJM. Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone/protein deacetylases. J. Biol. Chem., 278 (51), 50985–50998 (2003).
   PubMed Web of Science ®Google Scholar
• Smith BC , DenuJM. Mechanism-based inhibition of Sir2 deacetylases by thioacetyl-lysine peptide. Biochemistry46 (50), 14478–14486 (2007).
   PubMed Web of Science ®Google Scholar
• Hawse WF , HoffKG, FatkinsDGet al. Structural insights into intermediate steps in the Sir2 deacetylation reaction. Structure16 (9), 1368–1377 (2008).
   PubMed Web of Science ®Google Scholar
• Hu J , HeB, BhargavaS, LinH. A fluorogenic assay for screening Sirt6 modulators. Org. Biomol. Chem.11 (32), 5213–5216 (2013).
   PubMed Web of Science ®Google Scholar
• Tervo AJ , KyrylenkoS, NiskanenPet al. An in silico approach to discovering novel inhibitors of human sirtuin type 2. J. Med. Chem.47 (25), 6292–6298 (2004).
   PubMed Web of Science ®Google Scholar
• Audrito V , VaisittiT, RossiDet al. Nicotinamide blocks proliferation and induces apoptosis of chronic lymphocytic leukemia cells through activation of the p53/miR-34a/SIRT1 tumor suppressor network. Cancer Res.71 (13), 4473–4483 (2011).
   PubMed Web of Science ®Google Scholar
• Jung-Hynes B , NihalM, ZhongW, AhmadN. Role of sirtuin histone deacetylase SIRT1 in prostate cancer. A target for prostate cancer management via its inhibition?J. Biol. Chem.284 (6), 3823–3832 (2009).
   PubMed Web of Science ®Google Scholar
• Suzuki T , KhanMN, SawadaHet al. Design, synthesis, and biological activity of a novel series of human sirtuin-2-selective inhibitors. J. Med. Chem.55 (12), 5760–5773 (2012).
   PubMed Web of Science ®Google Scholar
• Taylor DM , BalabadraU, XiangZet al. A brain-permeable small molecule reduces neuronal cholesterol by inhibiting activity of sirtuin 2 deacetylase. ACS Chem. Biol.6 (6), 540–546 (2011).
   PubMed Web of Science ®Google Scholar
• Mai A , ValenteS, MeadeSet al. Study of 1,4-dihydropyridine structural scaffold: discovery of novel sirtuin activators and inhibitors. J. Med. Chem.52 (17), 5496–5504 (2009).
   PubMed Web of Science ®Google Scholar
• Alvala M , BhatnagarS, RaviAet al. Novel acridinedione derivatives: design, synthesis, SIRT1 enzyme and tumor cell growth inhibition studies. Bioorg. Med. Chem. Lett.22 (9), 3256–3260 (2012).
   PubMed Web of Science ®Google Scholar
• Alhazzazi TY , KamarajanP, JooNet al. Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer. Cancer117 (8), 1670–1678 (2011).
   PubMed Web of Science ®Google Scholar
• Smith BC , DenuJM. Acetyl-lysine analog peptides as mechanistic probes of protein deacetylases. J. Biol. Chem.282 (51), 37256–37265 (2007).
   PubMed Web of Science ®Google Scholar
• Fatkins DG , MonnotAD, ZhengW. Nepsilon-thioacetyl-lysine: a multi-facet functional probe for enzymatic protein lysine Nepsilon-deacetylation. Bioorg. Med. Chem. Lett.16 (14), 3651–3656 (2006).
   PubMed Web of Science ®Google Scholar
• Kiviranta PH , SuuronenT, WallenEAet al. N(epsilon)-thioacetyl-lysine-containing tri-, tetra-, and pentapeptides as SIRT1 and SIRT2 inhibitors. J. Med. Chem.52 (7), 2153–2156 (2009).
   PubMed Web of Science ®Google Scholar
• Jamonnak N , FatkinsDG, WeiL, ZhengW. N(epsilon)-methanesulfonyl-lysine as a non-hydrolyzable functional surrogate for N(epsilon)-acetyl-lysine. Org. Biomol. Chem.5 (6), 892–896 (2007).
   PubMed Web of Science ®Google Scholar
• Huhtiniemi T , SuuronenT, Lahtela-KakkonenMet al. N(epsilon)-Modified lysine containing inhibitors for SIRT1 and SIRT2. Bioorg. Med. Chem.18 (15), 5616–5625 (2010).
   PubMed Web of Science ®Google Scholar
• Chakrabarty SP , RamapanickerR, MishraR, ChandrasekaranS, BalaramH. Development and characterization of lysine based tripeptide analogues as inhibitors of Sir2 activity. Bioorg. Med. Chem.17 (23), 8060–8072 (2009).
   PubMed Web of Science ®Google Scholar
• Hirsch BM , HaoY, LiX, WesdemiotisC, WangZ, ZhengW. A mechanism-based potent sirtuin inhibitor containing Nepsilon-thiocarbamoyl-lysine (TuAcK). Bioorg. Med. Chem. Lett.21 (16), 4753–4757 (2011).
   PubMed Web of Science ®Google Scholar
• Jamonnak N , HirschBM, PangY, ZhengW. Substrate specificity of SIRT1-catalyzed lysine Nepsilon-deacetylation reaction probed with the side chain modified Nepsilon-acetyl-lysine analogs. Bioorg. Chem.38 (1), 17–25 (2010).
   PubMed Web of Science ®Google Scholar
• Suzuki T , AsabaT, ImaiE, TsumotoH, NakagawaH, MiyataN. Identification of a cell-active non-peptide sirtuin inhibitor containing N-thioacetyl lysine. Bioorg. Med. Chem. Lett.19 (19), 5670–5672 (2009).
   PubMed Web of Science ®Google Scholar
• Huhtiniemi T , SaloHS, SuuronenTet al. Structure-based design of pseudopeptidic inhibitors for SIRT1 and SIRT2. J. Med. Chem.54 (19), 6456–6468 (2011).
   PubMed Web of Science ®Google Scholar
• Mellini P , KokkolaT, SuuronenTet al. Screen of pseudopeptidic inhibitors of human sirtuins 1–3: two lead compounds with antiproliferative effects in cancer cells. J. Med. Chem.56 (17), 6681–6695 (2013).
   PubMed Web of Science ®Google Scholar
• Morimoto J , HayashiY, SugaH. Discovery of macrocyclic peptides armed with a mechanism-based warhead: isoform-selective inhibition of human deacetylase SIRT2. Angew. Chem. Int. Ed. Engl.51 (14), 3423–3427 (2012).
   PubMed Web of Science ®Google Scholar
• Grozinger CM , ChaoED, BlackwellHE, MoazedD, SchreiberSL. Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening. J. Biol. Chem.276 (42), 38837–38843 (2001).
   PubMed Web of Science ®Google Scholar
• Ota H , TokunagaE, ChangKet al. Sirt1 inhibitor, sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene25 (2), 176–185 (2006).
   PubMed Web of Science ®Google Scholar
• Peck B , ChenCY, HoKKet al. SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol. Cancer Ther.9 (4), 844–855 (2010).
   PubMed Web of Science ®Google Scholar
• Kojima K , OhhashiR, FujitaYet al. A role for SIRT1 in cell growth and chemoresistance in prostate cancer PC3 and DU145 cells. Biochem. Biophys. Res. Commun.373 (3), 423–428 (2008).
   PubMed Web of Science ®Google Scholar
• Jin KL , ParkJY, NohEJet al. The effect of combined treatment with cisplatin and histone deacetylase inhibitors on HeLa cells. J. Gynecol. Oncol.21 (4), 262–268 (2010).
   PubMed Web of Science ®Google Scholar
• Kalle AM , MallikaA, BadigerJ, Alinakhi, TalukdarP, Sachchidanand. Inhibition of SIRT1 by a small molecule induces apoptosis in breast cancer cells. Biochem. Biophys. Res. Commun.401 (1), 13–19 (2010).
   PubMed Web of Science ®Google Scholar
• Lara E , MaiA, CalvaneseVet al. Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect. Oncogene28 (6), 781–791 (2009).
   PubMed Web of Science ®Google Scholar
• Rotili D , TarantinoD, NebbiosoAet al. Discovery of salermide-related sirtuin inhibitors: binding mode studies and antiproliferative effects in cancer cells including cancer stem cells. J. Med. Chem.55 (24), 10937–10947 (2012).
   PubMed Web of Science ®Google Scholar
• Pasco MY , RotiliD, AltucciLet al. Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specific sirtinol analogues. J. Med. Chem.53 (3), 1407–1411 (2010).
   PubMed Web of Science ®Google Scholar
• Medda F , RussellRJ, HigginsMet al. Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. J. Med. Chem.52 (9), 2673–2682 (2009).
   PubMed Web of Science ®Google Scholar
• Uciechowska U , SchemiesJ, NeugebauerRCet al. Thiobarbiturates as sirtuin inhibitors: virtual screening, free-energy calculations, and biological testing. ChemMedChem3 (12), 1965–1976 (2008).
   PubMed Web of Science ®Google Scholar
• Bedalov A , GatbontonT, IrvineWP, GottschlingDE, SimonJA. Identification of a small molecule inhibitor of Sir2p. Proc. Natl Acad. Sci. USA98 (26), 15113–15118 (2001).
   PubMed Web of Science ®Google Scholar
• Pagans S , PedalA, NorthBJet al. SIRT1 regulates HIV transcription via Tat deacetylation. PLoS Biol.3 (2), e41 (2005).
   PubMed Web of Science ®Google Scholar
• Neugebauer RC , UchiechowskaU, MeierRet al. Structure–activity studies on splitomicin derivatives as sirtuin inhibitors and computational prediction of binding mode. J. Med. Chem.51 (5), 1203–1213 (2008).
   PubMed Web of Science ®Google Scholar
• Rotili D , TarantinoD, CarafaVet al. Benzodeazaoxaflavins as sirtuin inhibitors with antiproliferative properties in cancer stem cells. J. Med. Chem.55 (18), 8193–8197 (2012).
   PubMed Web of Science ®Google Scholar
• Rotili D , TarantinoD, CarafaVet al. Identification of tri- and tetracyclic pyrimidinediones as sirtuin inhibitors. ChemMedChem5 (5), 674–677 (2010).
   PubMed Web of Science ®Google Scholar
• Napper AD , HixonJ, McDonaghTet al. Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. J. Med. Chem.48 (25), 8045–8054 (2005).
   PubMed Web of Science ®Google Scholar
• Solomon JM , PasupuletiR, XuLet al. Inhibition of SIRT1 catalytic activity increases p53 acetylation but does not alter cell survival following DNA damage. Mol. Cell. Biol.26 (1), 28–38 (2006).
   PubMed Web of Science ®Google Scholar
• Stunkel W , PehBK, TanYCet al. Function of the SIRT1 protein deacetylase in cancer. Biotechnol. J.2 (11), 1360–1368 (2007).
   PubMedGoogle Scholar
• Zhang Q , ZengSX, ZhangYet al. A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol. Med.4 (4), 298–312 (2012).
   PubMed Web of Science ®Google Scholar
• Davis PD , HillCH, KeechEet al. Potent selective inhibitors of protein kinase C. FEBS Lett.259 (1), 61–63 (1989).
   PubMed Web of Science ®Google Scholar
• Trapp J , JochumA, MeierRet al. Adenosine mimetics as inhibitors of NAD+-dependent histone deacetylases, from kinase to sirtuin inhibition. J. Med. Chem.49 (25), 7307–7316 (2006).
   PubMed Web of Science ®Google Scholar
• Huber K , SchemiesJ, UciechowskaUet al. Novel 3-arylideneindolin-2-ones as inhibitors of NAD+ -dependent histone deacetylases (sirtuins). J. Med. Chem.53 (3), 1383–1386 (2010).
   PubMed Web of Science ®Google Scholar
• Suenkel B , FischerF, SteegbornC. Inhibition of the human deacylase sirtuin 5 by the indole GW5074. Bioorg. Med. Chem. Lett.23 (1), 143–146 (2013).
   PubMed Web of Science ®Google Scholar
• Cea M , SonciniD, FruscioneFet al. Synergistic interactions between HDAC and sirtuin inhibitors in human leukemia cells. PLoS ONE6 (7), e22739 (2011).
   PubMed Web of Science ®Google Scholar
• Schuetz A , MinJ, AntoshenkoTet al. Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin. Structure15 (3), 377–389 (2007).
   PubMed Web of Science ®Google Scholar
• Trapp J , MeierR, HongwisetD, KassackMU, SipplW, JungM. Structure-activity studies on suramin analogues as inhibitors of NAD+-dependent histone deacetylases (sirtuins). ChemMedChem2 (10), 1419–1431 (2007).
   PubMed Web of Science ®Google Scholar
• Lain S , HollickJJ, CampbellJet al. Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell13 (5), 454–463 (2008).
   PubMed Web of Science ®Google Scholar
• McCarthy AR , PirrieL, HollickJJet al. Synthesis and biological characterisation of sirtuin inhibitors based on the tenovins. Bioorg. Med. Chem.20 (5), 1779–1793 (2012).
   PubMed Web of Science ®Google Scholar
• Outeiro TF , KontopoulosE, AltmannSMet al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science317 (5837), 516–519 (2007).
   PubMed Web of Science ®Google Scholar
• Gey C , KyrylenkoS, HennigLet al. Phloroglucinol derivatives guttiferone G, aristoforin, and hyperforin: inhibitors of human sirtuins SIRT1 and SIRT2. Angew. Chem. Int. Ed. Engl.46 (27), 5219–5222 (2007).
   PubMed Web of Science ®Google Scholar
• Manjulatha K , SrinivasS, MulakayalaNet al. Ethylenediamine diacetate (EDDA) mediated synthesis of aurones under ultrasound: their evaluation as inhibitors of SIRT1. Bioorg. Med. Chem. Lett.22 (19), 6160–6165 (2012).
   PubMed Web of Science ®Google Scholar
• Garske AL , SmithBC, DenuJM. Linking SIRT2 to Parkinson's disease. ACS Chem. Biol.2 (8), 529–532 (2007).
   PubMed Web of Science ®Google Scholar
• Gutierrez M , AndrianasoloEH, ShinWKet al. Structural and synthetic investigations of tanikolide dimer, a SIRT2 selective inhibitor, and tanikolide seco-acid from the Madagascar marine cyanobacterium Lyngbya majuscula. J. Org. Chem.74 (15), 5267–5275 (2009).
   PubMed Web of Science ®Google Scholar
• Friden-Saxin M , SeifertT, LandergrenMRet al. Synthesis and evaluation of substituted chroman-4-one and chromone derivatives as sirtuin 2-selective inhibitors. J. Med. Chem.55 (16), 7104–7113 (2012).
   PubMed Web of Science ®Google Scholar
• Disch JS , EvindarG, ChiuCHet al. Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3. J. Med. Chem.56 (9), 3666–3679 (2013).
   PubMed Web of Science ®Google Scholar
• Knight ZA , ShokatKM. Chemical genetics: where genetics and pharmacology meet. Cell128 (3), 425–430 (2007).
   PubMed Web of Science ®Google Scholar
• Marks PA , BreslowR. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat. Biotech.25 (1), 84–90 (2007).
   PubMed Web of Science ®Google Scholar
• Wong S , McLaughlinJ, ChengD, ZhangC, ShokatKM, WitteON. Sole BCR-ABL inhibition is insufficient to eliminate all myeloproliferative disorder cell populations. Proc. Natl Acad. Sci. USA101 (50), 17456–17461 (2004).
   PubMed Web of Science ®Google Scholar
• Hopkins AL , MasonJS, OveringtonJP. Can we rationally design promiscuous drugs?Curr. Opin. Struct. Biol.16 (1), 127–136 (2006).
   PubMed Web of Science ®Google Scholar