sirtuin 2

Sirtuin modulator 2 (N-(3-(imidazo[2,1-b]thiazol-6-yl)phenyl)-2-methoxybenzamide) exhibits antidiabetic, anti-inflammatory and antitumor activities.

Sirtuin-IN-2 (compound 20) is an inhibitor of Sirtuin5, a key target in leukemia and breast cancer.

Resveratrol (SRT 501) is a polyphenolic natural product, a plant antitoxin with antioxidant and chemopreventive activities. Resveratrol has a wide range of targets including COX, SIRT, LOC, etc. Resveratrol induces autophagy and apoptosis.

Sirt2-IN-1 is an inhibitor of sirtuin 2 (IC50 = 163 nM).

Dihydrocoumarin (melilotin) is a compound found in Melilotus officinalis. Dihydrocoumarin is a yeast Sir2p inhibitor. Dihydrocoumarin also inhibits human SIRT1 and SIRT2 with IC50s of 208 μM and 295 μM, respectively.

JFD00244 is an inhibitor of sirtuin 2 (SIRT2). It has an anti-tumor effect.

Tenovin-6 is a p53 transcriptional activity agonist.

Inauhzin (INZ)(INZ) is a novel small molecule that effectively reactivates p53 by inhibiting SIRT1 activity, promotes p53-dependent apoptosis of human Y cells without causing apparently genotoxic stress(IC50=3 uM, in A549 cell).

Sirtinol is a selective SIRT1 2 inhibitor (IC50: 131 38 μM).

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

B2 (Linazolamide intermediate B impurity 2) promotes inclusion formation in cellular models of Huntington's disease and Parkinson's disease

AK-1 is a sirtuin 2 (SIRT2) inhibitor (IC50:12.5 µM).that prevents hippocampal neurodegeneration in Alzheimer's disease models and induces cell cycle arrest in colon carcinoma cells.

Benzamide, 3-methoxy-N-(3-thiazolo[5,4-b]pyridin-2-ylphenyl) (3-methoxy-N-(3-(thiazolo[5,4-b]pyridin-2-yl)phenyl)benzamide) is a sirtuin modulator and useful for increasing the lifespan of a cell, and treating and or preventing a wide variety of diseases and disorders including diabetes, cardiovascular disease, bloo

SirReal1-O-propargyl, a moiety based on SirReal1, is a selective and highly potent inhibitor of Sirtuin 2 (Sirt2), demonstrating an IC50 of 2.4 μM. It operates by binding to the cereblon ligand through a linker, facilitating the formation of PROTAC for the degradation of Sirt2[1].

Tenovin-1 inhibits protein-deacetylating activities of SirT1 and SirT2 and protects against MDM2-mediated p53 degradation, which involves ubiquitination.

AGK7 is an inactive control of AGK2, a selective SIRT2 inhibitor that selectively inhibits SIRT3 over SIRT1 and SIRT2 (IC50 = >5 μM, >50 μM and >50 μM for SIRT3, SIRT1, and SIRT2, respectively).

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).

Cambinol (SIRT1 2 Inhibitor IV) is a cell-permeable b-naphthol compound that inhibits the NAD-dependent deacetylase activity of SIRT1 2 (IC50: 56 59 μM, respectively) in a substrate-, but not NAD-, competitive manner. Cambinol inhibits SIRT5 deacetylase activity only at much higher concentrations (IC50 >300 μM) and no inhibitory for the class I and II HDACs. In BCL6-expressing Burkitt lymphoma cell lines, Cambinol-induced apoptosis has been attributed to the hyperacetylation of p53 and BCL6.Cambinol is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor)

WAY-270360 (N-[4-(1H-benzimidazol-2-yl)phenyl]-2,4-dimethoxybenzamide) is a sirtuin modulator and an epidermal growth factor receptor (EGFR) inhibitor.

AGK2(IC50=3.5 μM) is an effective, and specific SIRT2 inhibitor.

SirReal2 is a potent and selective Sirt2 inhibitor with IC50 of 140 nM.

Nicotinamide Hydrochloride, a form of vitamin B3 (niacin), inhibits sirtuin 2 (SIRT2) activity in vitro with an EC50 of 2 μM, reducing melanoma cell number by up to 90% and increasing cellular NAD+, ATP, and ROS levels. It also inhibits tumor growth in vivo and improves survival in melanoma-bearing mice, making it useful for skin cancer research, including melanoma.

Tenovin-6 Hydrochloride is an SIRT1, SIRT2 and HDAC8 inhibitor(IC50s of 21 μM, 10 μM, and 67 μM for SirT1, SirT2, and SirT3, respectively), and is also a potent p53 activator .

FLS-359, a selective and orally active allosteric modulator for sirtuin 2, has an IC50 of 3 μM. It displays antiviral activity against both RNA and DNA viruses by inhibiting DNA RNA replication [1].