sirt1 in 1

SIRT1-IN-1 is a selective inhibitor of SIRT1 with an IC50 of 205 nM. SIRT1-IN-1 is an inhibitor of cytomegalovirus (CMV) with antiviral activity.

Sirt1 2-IN-1 (Compound 7) is an inhibitor of SIRT1 and SIRT2, with IC50 values of 1.81 μg mL for SIRT1, 2.10 μg mL for SIRT2, and 20.5 μg mL for SIRT3, and exhibits α-microtubulin hyperacetylation activity, demonstrating significant anticancer effects.

SIRT1 2 3-IN-1 (compound 10) is a potent, selective, and cell-permeable inhibitor targeting SIRT1, SIRT2, and SIRT3, with inhibitory concentrations (IC50s) of 0.54 μM, 0.253 μM, and 0.72 μM, respectively. It is utilized in cancer research [1].

CAY10602 is a SIRT1 activator derived from high throughput screening for compounds that enhance SIRT1-mediated deacetylation of a SIRT1-specific substrate. Functional assays indicate that CAY10602 dose-dependently suppresses NF-κB-dependent induction of TNF-α by lipopolysaccharide in THP-1 cells, achieving approximately 75% inhibition at 60 μM without cytotoxicity.

SIRT-IN-1 is a potent inhibitor of SIRT1, SIRT2, and SIRT3, with IC50 values of 15, 10, and 33 μM, respectively

SIRT-IN-2 is a potent SIRT1 2 3 inhibitor [IC50s of 4, 1, and 7 μM, respectively].

KL1333 (NQO1 activator 1) enhances energy metabolism and mitochondrial dysfunction in MELAS fibroblasts. Elevated NAD+ levels trigger the activation of SIRT1 and AMPK, and subsequently activates PGC-1α. NQO1 activator 1 is an orally available NAD+ modulator. It reacts with NAD(P)H: NQO1 as a substrate, resulting in increases in intracellular NAD+ levels via NADH oxidation.

LDH-IN-3 (compound E38) is an inhibitor of lactate dehydrogenase (LDH) and a potential protective agent against ischemic neuronal damage in the eyes and brain. It functions through the HO-1 SIRT1 pathway.

Sirtuins (SIRTs) represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs). Human SIRT1 is the homolog of yeast silent information regulator 2 (Sir2) and has been shown to regulate the activity of the p53 tumor suppressor and inhibit apoptosis. Small molecule activators of SIRT1, such as resveratrol, extend lifespan in yeast and C. elegans in a manner that resembles caloric restriction. CAY10591 has been identified as an activator of the enzyme SIRT1. This compound increases fluorescence by 233% in a SIRT1 activity assay. [Activator activity was defined as the percentage of signal increase relative to signal window in the following formula: 100 x (Sample - Signallow)/(Signalhigh - Signallow)]. CAY10591 suppresses TNF-α in a dose-dependent manner. In THP-1 cells, TNF-α levels decreased from 325 pg/ml (control) to 104 and 53 pg/ml with 20 and 60 µM CAY10591, respectively. This activator also has a significant dose-dependent effect on fat mobilization in differentiated adipocytes, which would indicate the potential of SIRT1 activators for anti-obesity or anti-diabetic purposes.

Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988). Alaproclate is a selective serotonin reuptake inhibitor (SSRI).1,2 It inhibits depletion of serotonin (5-HT) induced by 4-methyl-α-ethyl-m-tyramine in rat cerebral cortex, hippocampus, hypothalamus, and striatum (EC50s = 18, 4, 8, and 12 mg/kg, respectively).1 Alaproclate inhibits NMDA-evoked currents and depolarization-induced voltage-dependent potassium currents in rat hippocampal neurons (IC50s = 1.1 and 6.9 μM, respectively) and does not inhibit GABA-evoked currents when used at concentrations up to 100 μM.2 It increases sirtuin 1 (SIRT1) levels in N2a murine neuroblastoma cells expressing apolipoprotein E4 (ApoE4; IC50 = 2.3 μM) and in the hippocampus in the FXFAD-ApoE4 transgenic mouse model of Alzheimer's disease when administered at a dose of 20 mg/kg twice daily.3 Alaproclate (40 mg/kg) decreases immobility time in the forced swim test in rats, indicating antidepressant-like activity.4 References1. Michael, G.B., Eidam, C., Kadlec, K., et al. Increased MICs of gamithromycin and tildipirosin in the presence of the genes erm(42) and msr(E)-mph(E) for bovine Pasteurella multocida and Mannheimia haemolytica. Journal of Antimicrobial Chemotherapy 67(6), 1555-1557 (2012).2. Svensson, B.E., Werkman, T.R., and Rogawski, M.A. Alaproclate effects on voltage-dependent K+ channels and NMDA receptors: Studies in cultured rat hippocampal neurons and fibroblast cells transformed with Kv1.2 K+ channel cDNA. Neuropharmacology 33(6), 795-804 (1994).3. Campagna, J., Soilman, P., Jagodzinska, B., et al. A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model. Sci. Rep. 8(1), 17574 (2018).4. Danysz, W.P., A., Kostowski, W., Malatynska, E., et al. Comparison of desipramine, amitriptyline, zimeldine and alaproclate in six animal models used to investigate antidepressant drugs. Pharmacol. Toxicol. 62(1), 42-50 (1988).

OSS_128167 (SIRT6-IN-1) is a specific SIRT6 inhibitor, and for SIRT6(IC50=89 μM), SIRT1(IC50=1578 μM) and SIRT2(IC50=751 μM).

SIRT-IN-3, a potent inhibitor of SIRT1 with an IC50 value of 17 μM, exhibits approximate 4-fold and 14-fold greater selectivity for SIRT1 over SIRT2 and SIRT3, with respective IC50 values of 74 μM for SIRT2 and 235 μM for SIRT3 [1].

SIRT1-IN-2 (compound 3h) is a potent and selective inhibitor of SIRT1 (silent information regulator 1) with an IC50 of 1.6 μM [1].

SIRT1-IN-3 (compound 3j) is a potent and selective inhibitor of silent information regulator 1 (SIRT1) with an IC50 of 4.2 μM [1].

Nicotinamide-d4 is intended for use as an internal standard for the quantification of nicotinamide by GC- or LC-MS. Nicotinamide is an amide form of niacin, which is also known as vitamin B3, that can be biosynthesized in vivo or obtained through the diet. It is a precursor in the synthesis of the metabolic cofactor NAD+ and an inhibitor of sirtuin 1 (SIRT1; IC50 = <50 µM). Nicotinamide (10 µM) increases the activity of serine palmitoyltransferase (SPT) and the biosynthesis of ceramide, glucosylceramide, sphingomyelin, free fatty acids, and cholesterol in primary human keratinocytes. Nicotinamide (40 µM) induces apoptosis in SNU-398, SNU-739, and HepG2 hepatocellular carcinoma (HCC) cells, and it prevents the formation of neoplastic lesions in a diethylnitrosamine-induced mouse model of HCC. Unlike niacin, nicotinamide does not reduce plasma lipid levels or induce flushing.

Sirtuin Modulator 5, a sirtuin modulating agent, activates SIRT1 with an efficacy marked by a DC50 value of less than 50 μM. It is applicable in enhancing cell longevity and is researched for its therapeutic potential in a wide range of diseases such as those associated with aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular diseases, blood clotting disorders, inflammation, cancer, and flushing. Furthermore, it holds promise for conditions that could benefit from boosted mitochondrial activity [1].

BML-278 is a SIRT1 activator with an EC150 of 1 μM. It increases H3K9 methylation and inhibits H3K9 acetylation in parental and maternal prokaryotes, improving early embryonic development. BML-278 induces cell cycle arrest at the G1 S phase in primary human mesenchymal stromal cells, delaying senescence. It also reduces microtubule protein acetylation in U937 cells and increases mitochondrial density in mouse C2C12 myoblasts.

Sirt1 2-IN-2 (compound hsa55) is a dual inhibitor, targeting SIRT1 with an IC50 of 1.8 μM and SIRT2 with an IC50 of 2.4 μM. It effectively inhibits p53 deacetylation while enhancing the acetylation of p53 and α-tubulin, promoting apoptosis and exhibiting anti-proliferative effects on human leukemia cell lines [1].

Sirt1 2-IN-3 (compound PS9) serves as a dual inhibitor of SIRT1 2, exhibiting IC50 values of 1.4 μM (SIRT1) and 2.0 μM (SIRT2), respectively. This compound effectively inhibits p53 deacetylation while simultaneously elevating p53 and α-tubulin acetylation levels. Additionally, Sirt1 2-IN-3 promotes apoptosis and exhibits antiproliferative effects on human leukemia cell lines [1].

Sirt1 2-IN-4 (compound PS3) is a potent triple inhibitor of SIRT1, SIRT2, and SIRT3, exhibiting IC50 values of 1.2 μM (SIRT1), 1.9 μM (SIRT2), and 18.6 μM (SIRT3), respectively. It effectively inhibits p53 deacetylation, indicating potential anticancer properties [1].

SIRT1 Activator 1 (Compound 3), a marine-derived xyloallenoide A derivative from the Xylaria sp. mangrove fungus, exhibits angiogenic effects in zebrafish and protects human endothelial progenitor cells (hEPCs) from AngII-induced senescence. It achieves this by elevating SIRT1 expression and modulating the AMPK Akt signaling pathway [1].

10m ZS44, a blood-brain barrier-permeable Glioblastoma (GBM) inhibitor, significantly suppresses tumor growth in mouse xenograft models and induces apoptosis through activation of the SIRT1 p53-mediated pathway, thereby reducing U251 cell proliferation [1].