sirt1-in-1

SIRT1-IN-1 是一种选择性的 SIRT1 抑制剂，IC50值为 205 nM。 SIRT1-IN-1 是一种具有抗病毒活性的巨细胞病毒 (CMV) 抑制剂。

CAY10602 是一种SIRT1激活剂，可剂量依赖性地抑制 THP-1 细胞中脂多糖对 TNF-α 的 NF-κB 依赖性诱导。

SIRT-IN-1 是一种有效SIRT1 2 3抑制剂，IC50分别为 15，10，33 μM。

SIRT-IN-2 是一种 SIRT1 2 3 有效抑制剂，IC50 分别为 4、1和 7 μM。

KL1333 (NQO1 activator 1) 是口服NAD+调节剂，与 NAD(P)H: 醌氧化还原酶 1 作为底物反应。它改善线粒体脑肌病、乳酸酸中毒和中风样发作成纤维细胞的能量代谢和线粒体功能障碍。它对顺铂诱导的小鼠耳蜗培养耳毒性的保护作用。

LDH-IN-3 (compound E38)，作为乳酸脱氢酶 (LDH) 的抑制剂，具备治疗眼部及脑部缺血性神经损伤的潜力。该化合物通过HO-1 SIRT1途径实现其保护作用。

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) 是一种选择性沉默调节蛋白 6 (SIRT6) 抑制剂，对 SIRT6，SIRT1 和 SIRT2 的 IC50分别为 89 μM，1578 μM 和 751 μM。它具有抗 HBV、抗癌、抗炎和抗病毒活性，可抑制 HBV 的转录和复制。

SIRT-IN-3 是一种有效的SIRT 抑制剂，对 SIRT1 的IC50为 17 μM。SIRT-IN-3 对 SIRT1 的选择性分别是 SIRT-2 和 SIRT3 的 4 倍和 14 倍，其对 SIRT2的IC50为74 μM；对SIRT3的IC50为235 μM。

SIRT1-IN-2 (compound 3h) 是一种有效的选择性SIRT1（沉默信息调节因子1）抑制剂，IC50值为 1.6 μM。

SIRT1-IN-3 (compound 3j) 是一种有效且选择性的沉默信息调节因子 1 (SIRT1)抑制剂，IC50值为 4.2 μM。

Sirt1 2-IN-1 (Compound 7) 是一种 SIRT1 和 SIRT2 的抑制剂， 能够作用于 SIRT1 (IC50: 1.81 μg mL)、SIRT2 (IC50: 2.10 μg mL) 和 SIRT3 (IC50: 20.5 μg mL)，并具有α-微管蛋白的超乙酰化活性 (IC50: 32.05 μg mL)。Sirt1 2-IN-1 表现出显著的抗癌作用。

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.

Sirtuinmodulator 5 是一种sirtuin 调节剂。Sirtuinmodulator 5 可以激活SIRTl，DC50值 <50 μM。Sirtuinmodulator 5 可用于增加细胞的寿命并用于研究多种疾病，包括例如与衰老或压力、糖尿病、肥胖症、神经退行性疾病、心血管疾病、凝血障碍、 炎症、癌症和 或潮红以及将受益于线粒体活性增加的疾病或病症。

SIRT1 2 3-IN-1 (compound 10) 为高效、选择性并具细胞渗透性的 SIRT1 2 3 抑制剂，其对 SIRT1、SIRT2 和 SIRT3 的 IC50 值分别为 0.54、0.253、0.72 μM，适用于癌症研究。

BML-278 是一种 SIRT1 激活剂 ，EC150 值为 1 μM。BML-278 增加父本和母本原核中的 H3K9 甲基化并抑制 H3K9 乙酰化，可用于改善早期胚胎发育。BML-278 促使原代人间充质细胞的细胞周期停止在 G1 S 期，可用于延缓衰老。BML-278 减少 U937 细胞中的微管蛋白乙酰化，增加小鼠 C2C12 成肌细胞的线粒体密度。

Sirt1 2-IN-2 (compound hsa55)是一种针对SIRT1 2的双重抑制剂，具有分别针对SIRT1和SIRT2的IC50值为1.8 μM和2.4 μM。该化合物能有效阻止p53的脱乙酰化作用，并提高p53及α-微管蛋白的乙酰化水平。此外，Sirt1 2-IN-2能诱导细胞凋亡，并展示出对人白血病细胞系的抗增殖效果。

Sirt1 2-IN-3 (compound PS9) 作为SIRT1 2的双重抑制剂，其对SIRT1和SIRT2的IC50值分别为1.4 μM 和 2.0 μM。该化合物能够有效抑制p53脱乙酰化，并提升p53与α-微管蛋白的乙酰化水平。Sirt1 2-IN-3还能诱导细胞凋亡，并展现对人白血病细胞系的抗增殖效果。

Sirt1 2-IN-4（compound PS3）为SIRT1 2 3抑制剂，其IC50分别为1.2 μM (SIRT1)、1.9 μM (SIRT2) 和2.0 μM (SIRT3)。该化合物能完全阻制p53脱乙酰化作用，显示出潜在的抗癌活性。

SIRT1 activator1(compound 3)，作为海洋化合物xyloallenoide a的衍生物，最初从红树林真菌Xylaria sp中分离获得。该化合物在斑马鱼模型中展现了促进血管生成的活性，并且能够通过提升SIRT1的表达水平以及调节AMPK Akt信号通路，来防护人类内皮祖细胞(hEPC)免受血管老化的影响。

10m ZS44是一种能够穿透血脑屏障的Glioblastoma (GBM) 抑制剂，在小鼠异种移植模型中有效抑制了GBM肿瘤生长，并通过激活SIRT1 p53介导的细胞凋亡途径来抑制U251细胞增殖。

AdipoR agonist 1 (Compound 112254) 作为脂联素受体 (AdipoR) 的激动剂，能够激活多种关键转录调节因子，包括过氧化物酶体增殖激活受体 (PPAR)、过氧化物酶体增殖激活受体γ 辅激活因子 1α (PGC-1α)、sirtuin 1 (SIRT1) 以及腺苷酸活化蛋白激酶 (AMPK)。此化合物主要用于预防性兴奋剂的研究领域。