Sirtuin

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.

Nicotinamide riboside increases NAD[+] levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities.

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

SRT 1720 is a selective activator of SIRT1 (EC1.5: 0.16 μM) and shows less potent activities on SIRT2 (EC1.5: 37 μM) and SIRT3 (EC1.5: 300 μM).

MC2184 is the inhibitor of human recombinant SIRT1.

WAY-323061 is a SIRT2 inhibitor.

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

SIRT6-IN-5（SIRT6 inhibitor 5） is a potent and selective SIRT6 inhibitor with an IC50 value of 34 μM.SIRT6-IN-5 is immunosuppressive and chemo-sensitizing, increases H3K9 acetylation and glucose uptake in cultured cells, and reduces T-cell proliferation.

SIRT5 inhibitor 1 is a potent and selective inhibitor of human Sirtuin 5 deacylase (IC50: 0.11 μM). sIRT5 inhibitor 1 is associated with ageing-related diseases.

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

JGB1741 (ILS-JGB-1741) is a potent and selective inhibitor of SIRT1 with an IC50 of 15 μM. JGB1741 modulates Bax/Bcl2 ratio, cytochrome c release and PARP cleavage and increases the acetylated p53 levels leading to p53-mediated apoptosis. JGB1741 can be used in studies about breast cancer.

RK-9123016 is a SIRT2 inhibitor. RK-9123016 increases the acetylation level of eukaryotic translation initiation factor 5A (eIF5A), a physiological substrate of SIRT2, and reduces cell viability of human breast cancer cells accompanied with a decrease in c-Myc expression.

MC3482 is a specific inhibitor of sirtuin5 (SIRT5).

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.

Scopolin (Scopoloside) formation is increased by the enhanced activity of PAL. Scopolin can reduce the clinical symptoms of rat AIA by inhibiting inflammation and angiogenesis, and this compound may be a potent agent for angiogenesis related diseases and can serve as a structural base for screening more potent synthetic analogs.

3-TYP (3-(1H-1,2,3-triazol-4-yl) pyridine) is a selective SIRT3 inhibitor.

Fisetin is a natural flavonol extracted from Rhus succedanea L that is structurally and functionally related to kaempferol, can modulate sirtuins,with antioxidant, anticancer, neuroprotection effects.

Suramin Sodium Salt (BAY-205) is a sodium salt form of suramin, a polysulphonated naphthylurea with potential antineoplastic activity. Suramin blocks the binding of various growth factors, including insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor growth factor-beta (TGF-beta), to their receptors, thereby inhibiting endothelial cell proliferation and migration. This agent also inhibits vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis; retroviral reverse transcriptase; uncoupling of G-proteins from receptors; topoisomerases; cellular folate transport; and steroidogenesis.

Epigenetic factor-IN-1 (40569Z) is an epigenetic factor inhibitor that exhibits potent binding affinity for SIRT7. It is utilized in the study of liver cancer [1].

Sirtuin-1 inhibitor 1 is an inhibitor against deacetylase-1 (Sirtuin-1) and can be used to study senescence and cell death in the organism.

MDL-811, an allosteric activator of SIRT6, markedly enhances the deacetylation of histone H3 at lysine residues 9, 18, and 56 (H3K9Ac, H3K18Ac, and H3K56Ac), presenting potential utility in colorectal cancer research [1].

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

SIRT6-IN-3 (compound 8a), a selective SIRT6 inhibitor (IC50 = 7.49 μM), impedes the proliferation of pancreatic ductal adenocarcinoma (PDAC) cells and prompts apoptosis. It enhances the responsiveness of cancer cells to gemcitabine by obstructing the DNA damage repair pathway, thus serving as a valuable tool in pancreatic cancer research [1].

(+)-Syringaresinol shows antioxidant potential, it exhibits cytoprotective activity in cultured MCF-7 cells stressed by H2O2.

YK-3-237 (B-[2-Methoxy-5-[(1E)-3-oxo-3-(3,4,5-trimethoxyphenyl)-1-propen-1-yl]phenyl]boronic acid) reduces acetylation of mtp53 and exhibits anti-proliferative effects toward triple-negative breast cancer (TNBC) cells carrying mtp53.

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

MIND4-19 is an inhibitor of SIRT2 with antitumor activity.

PROTAC Sirt2 Degrader-1 is a SirReal-based PROTAC, acts as a Sirt2 degrader, composed of a highly potent and isotype-selective Sirt2 inhibitor, a linker, and a bona fide cereblon ligand for E3 ubiquitin ligase. PROTAC Sirt2 Degrader-1 shows an IC50 of 0.25 μM for Sirt2, with no effect on Sirt1/Sirt3 (IC50s > 100 μM)[1].

YM-08 (Compound 7a), a brain-penetrant SIRT2 inhibitor, exhibits an IC50 of 19.9 μM. Additionally, it acts as an inhibitor of Hsp70 [1].

Z26395438 is an inhibitor of Sirtuin-1 with IC50 of 1.6 μM.

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.

Selisistat S-enantiomer (EX-527 S-enantiomer) is an effective and specific SIRT1 inhibitor (IC50 = 98 nM) and shows >200-fold selectivity against SIRT2/3.

WAY-354574 is an active compound that targets the deacetylase Sirtuin, utilized in research focused on Huntington's disease (HD) [1].

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

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].

HSP70/SIRT2-IN-1 (Compound 2a) serves as a dual inhibitor targeting both SIRT2 and HSP70, exhibiting an IC50 of 17.3±2.0 μM against SIRT2. This compound possesses antitumor activity [1].

SIRT5 inhibitor 9 (compound 14), with an IC50 of 4.07 μM, is a competitive inhibitor of the sirtuin SIRT5, exhibiting potential anticancer properties [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].

Sirt1/2-IN-2 (compound hsa55) serves as a dual inhibitor for SIRT1 with an IC50 of 1.8 μM and SIRT2 with an IC50 of 2.4 μM, respectively. It effectively inhibits p53 deacetylation while enhancing the acetylation of p53 and α-tubulin. The compound also promotes apoptosis and exhibits anti-proliferative effects on human leukemia cell lines [1].

SIRT5 inhibitor 8 (compound 10) serves as a competitive inhibitor of sirtuin SIRT5, exhibiting an IC50 of 5.38 μM, and possesses anticancer potential [1].

Ophiopogonin D' can activate SIRT1 in a dose-dependent manner. Ophiopogonin D' also noncompetitively inhibits UGT1A6 and UGT1A10.

SRT3657 is a brain-permeable SIRT1 activator, has neuroprotective effect.

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)

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 .

Et-29 is a selective inhibitor of SIRT5 inhibitor with a Ki of 40 nM.

SIRT7 inhibitor 97491 is an HDAC inhibitor with high specificity for SIRT7 (IC50 = 325 nM). SIRT7 inhibitor 97491 promotes apoptosis through caspase pathway.

1. Agrimol B is a main active ingredient isolated from Agrimonia pilosa Ledeb.

SPC-180002, a dual SIRT1/3 inhibitor, exhibits IC50 values of 1.13 and 5.41 μM for SIRT1 and SIRT3, respectively. It disrupts redox homeostasis through ROS generation, consequently enhancing p21 protein stability and inducing mitochondrial dysfunction. Furthermore, this compound significantly impedes cell cycle progression and malignancy proliferation, while also activating the Nrf2 signaling pathway [1].

SIRT5 inhibitor 7 (compound 58), a selective and substrate-competitive SIRT5 inhibitor, exhibits anti-inflammatory properties by modulating protein succinylation and attenuating pro-inflammatory cytokine release. It demonstrates renal protective effects and is active in vivo, showing efficacy in AKI mouse models subjected to lipopolysaccharide (LPS) and cecal ligation/perforation (CLP)-induced sepsis-related acute kidney injury [1].