1. Discovery of thieno[3,2-d]pyrimidine-6-carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3.

    Journal of medicinal and pharmaceutical chemistry 56(9):3666 (2013) PMID 23570514

    The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA enc...
  2. Discovery of thieno[3,2-d]pyrimidine-6-carboxamides as potent inhibitors of SIRT1, SIRT2, and SIRT3.

    Journal of medicinal and pharmaceutical chemistry 56(9):3666 (2013) PMID 23570514

    The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA enc...
  3. Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man.

    British Journal of Clinical Pharmacology 75(1):186 (2013) PMID 22616762 PMCID PMC3555058

    SRT2104 is a novel, first-in-class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SRT2104 was dosed to healthy male and female volunteers in a series of phase 1 clinical studies that were designed to elucidate tolerability and pharmacokinetics associated wit...
  4. Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man.

    British Journal of Clinical Pharmacology 75(1):186 (2013) PMID 22616762 PMCID PMC3555058

    SRT2104 is a novel, first-in-class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SRT2104 was dosed to healthy male and female volunteers in a series of phase 1 clinical studies that were designed to elucidate tolerability and pharmacokinetics associated wit...
  5. Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators.

    Bioorganic & Medicinal Chemistry Letters 19(8):2350 (2009) PMID 19303289

    SIRT1 is an NAD(+)-dependent protein deacetylase that appears to produce beneficial effects on metabolic parameters such as glucose and insulin homeostasis. Activation of SIRT1 by resveratrol (1) has been shown to modulate insulin resistance, increase mitochondrial content and prolong survival i...
  6. Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators.

    Bioorganic & Medicinal Chemistry Letters 19(8):2350 (2009) PMID 19303289

    SIRT1 is an NAD(+)-dependent protein deacetylase that appears to produce beneficial effects on metabolic parameters such as glucose and insulin homeostasis. Activation of SIRT1 by resveratrol (1) has been shown to modulate insulin resistance, increase mitochondrial content and prolong survival i...
  7. Discovery of imidazo[1,2-b]thiazole derivatives as novel SIRT1 activators.

    Journal of medicinal and pharmaceutical chemistry 52(5):1275 (2009) PMID 19199480

    A series of imidazo[1,2-b]thiazole derivatives is shown to activate the NAD(+)-dependent deacetylase SIRT1, a potential new therapeutic target to treat various metabolic disorders. This series of compounds was derived from a high throughput screening hit bearing an oxazolopyridine core. Water-so...
  8. Discovery of imidazo[1,2-b]thiazole derivatives as novel SIRT1 activators.

    Journal of medicinal and pharmaceutical chemistry 52(5):1275 (2009) PMID 19199480

    A series of imidazo[1,2-b]thiazole derivatives is shown to activate the NAD(+)-dependent deacetylase SIRT1, a potential new therapeutic target to treat various metabolic disorders. This series of compounds was derived from a high throughput screening hit bearing an oxazolopyridine core. Water-so...
  9. Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators

    Bioorganic & Medicinal Chemistry Letters 19(8):2350 (2009) PMID 19303289

    The identification and SAR of novel small molecule activators of SIRT1, which are structurally distinct and more potent than resveratrol ( 1), are described.
  10. Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo.

    BMC Systems Biology 3:31 (2009) PMID 19284563 PMCID PMC2660283

    Calorie restriction (CR) produces a number of health benefits and ameliorates diseases of aging such as type 2 diabetes. The components of the pathways downstream of CR may provide intervention points for developing therapeutics for treating diseases of aging. The NAD+-dependent protein deacetyl...
  11. Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators

    Bioorganic & Medicinal Chemistry Letters 19(8):2350 (2009)

    The identification and SAR of novel small molecule activators of SIRT1, which are structurally distinct and more potent than resveratrol ( 1), are described.
  12. Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo.

    BMC Systems Biology 3:31 (2009) PMID 19284563 PMCID PMC2660283

    Calorie restriction (CR) produces a number of health benefits and ameliorates diseases of aging such as type 2 diabetes. The components of the pathways downstream of CR may provide intervention points for developing therapeutics for treating diseases of aging. The NAD+-dependent protein deacetyl...
  13. Sirtuins--novel therapeutic targets to treat age-associated diseases.

    Nature Reviews: Drug Discovery 7(10):841 (2008) PMID 18827827

    Sirtuins post-translationally modulate the function of many cellular proteins that undergo reversible acetylation-deacetylation cycles, affecting physiological responses that have implications for treating diseases of ageing. Potent small-molecule modulators of sirtuins have shown efficacy in pr...
  14. Sirtuins--novel therapeutic targets to treat age-associated diseases.

    Nature Reviews: Drug Discovery 7(10):841 (2008) PMID 18827827

    Sirtuins post-translationally modulate the function of many cellular proteins that undergo reversible acetylation-deacetylation cycles, affecting physiological responses that have implications for treating diseases of ageing. Potent small-molecule modulators of sirtuins have shown efficacy in pr...
  15. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.

    Nature 450(7170):712 (2007) PMID 18046409 PMCID PMC2753457

    Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeost...
  16. Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity?

    Experimental Gerontology 41(8):718 (2006) PMID 16842957 PMCID PMC3366689

    Eukaryotes have evolved elaborate mechanisms to survive periods of adversity. By manipulating genes that control these mechanisms, researchers have found they can generate more stress resistant, longer-lived organisms. One of these is the PNC1 gene of Saccharomyces cerevisiae, a master "longevit...
  17. Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity?

    Experimental Gerontology 41(8):718 (2006) PMID 16842957 PMCID PMC3366689

    Eukaryotes have evolved elaborate mechanisms to survive periods of adversity. By manipulating genes that control these mechanisms, researchers have found they can generate more stress resistant, longer-lived organisms. One of these is the PNC1 gene of Saccharomyces cerevisiae, a master "longevit...
  18. Nampt/PBEF/Visfatin: A regulator of mammalian health and longevity?

    Experimental Gerontology 41(8):718 (2006)

    Eukaryotes have evolved elaborate mechanisms to survive periods of adversity. By manipulating genes that control these mechanisms, researchers have found they can generate more stress resistant, longer-lived organisms. One of these is the PNC1 gene of Saccharomyces cerevisiae,...
  19. Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors.

    Journal of Medicinal Chemistry 48(24):7789 (2005) PMID 16302818

    In a search for potent inhibitors of class III histone/protein deacetylases (sirtuins), a series of sirtinol analogues have been synthesized and the degree of inhibition was assessed in vitro using recombinant yeast Sir2, human SIRT1, and human SIRT2 and in vivo with a yeast phenotypic assay. Tw...
  20. Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors.

    Journal of Medicinal Chemistry 48(24):7789 (2005) PMID 16302818

    In a search for potent inhibitors of class III histone/protein deacetylases (sirtuins), a series of sirtinol analogues have been synthesized and the degree of inhibition was assessed in vitro using recombinant yeast Sir2, human SIRT1, and human SIRT2 and in vivo with a yeast phenotypic assay. Tw...