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 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].

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].

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

Sirt1/2-IN-1 (Compound 7) is an inhibitor of SIRT1 and SIRT2 and is capable of acting on SIRT1 (IC50: 1.81 μg/mL), SIRT2 (IC50: 2.10 μg/mL) and SIRT3 (IC50: 20.5 μg/mL) and has α-microtubulin hyperacetylation activity ( Sirt1/2-IN-1 exhibited significant anticancer effects.

SIRT1-IN-3 (compound 3j) is a potent and selective inhibitor of silent information regulator 1 (SIRT1) with an IC 50 of 4.2 μM [1].

SIRT1-IN-2 (compound 3h) is a potent and selective inhibitor of SIRT1 (silent information regulator 1) with an IC 50 of 1.6 μM [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-A2 is a SIRT1 activator.

SIRT1/2 Inhibitor IV (cannabinol) is a small-molecule inhibitor of SIRT1 and SIRT2 with IC50 values of 56 μM and 59 μM, respectively.

SIRT1-I5 is a SIRT1 inhibitor. It shows a potent effect on the prostate cancer cell line.

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)

LDN-0028574 is a SIRT1 inhibitor that also acts as an inhibitor of the human MDM2-p53 interaction.

Butein (2’,3,4,4’-tetrahydroxy Chalcone), a plant polyphenol, is isolated from Rhus verniciflua. It can inhibit the activation of protein tyrosine kinase, NF-κB and STAT3, and also can inhibit EGFR.

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

Quercetin Dihydrate (Sophoretin) is a polyphenolic flavonoid that was found in a wide variety of plant-based foods, such as apples, onions, berries, and red wine. It is used for their nervous system and anticancer effects.

Quercetin, a flavonoid natural product, is a SIRT1 activator. It is also a PI3K inhibitor, inhibiting PI3Kγ, PI3Kδ, and PI3Kβ with IC50 values of 2.4, 3.0, and 5.4 μM, respectively. Recognized as a heat shock protein inhibitor, Quercetin can significantly reduce exosome release in TII models by downregulating Hsp70 or Hsp90.

MC2184 is the inhibitor of human recombinant SIRT1.

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).

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.

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.

Suramin is a reversible, competitive inhibitor of protein-tyrosine phosphatases (PTPases) [1], demonstrating potent inhibition against sirtuins: SirT1 (IC50=297 nM), SirT2 (IC50=1.15 μM), and SirT5 (IC50=22 μM) [2]. It also acts as a competitive inhibitor of reverse transcriptase (DNA topoisomerase II: IC50=5 μM) [3] [4] and exhibits potent inhibition of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) [5]. Additionally, Suramin effectively inhibits IP5K, showcasing its antiparasitic, anti-neoplastic, and anti-angiogenic properties [6] [7] [8].

Nicotinamide riboside tartrate (NRT) is an oral NAD+ precursor that raises NAD+ levels, activates SIRT1 and SIRT3, and serves as a vitamin B3 (niacin) source. NRT also improves oxidative metabolism and protects against metabolic abnormalities induced by a high-fat diet. Furthermore, NRT mitigates cognitive decline in a transgenic mouse model of Alzheimer's disease.

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].

3β,6α,12β-Dammar-E-20(22)-ene-3,6,12,25-tetraol is a compound that functions as a SIRT1 activator, effectively enhancing SIRT1 activity. Additionally, it demonstrates notable anti-tumor properties.

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 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].

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].

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].

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.

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.

ZINC08792355 is a novel inhibitor of SIRT1.

SRTCX1002 is a SIRT1 Activator Suppressing Inflammatory Responses through Promotion of p65 Deacetylation and NF-κB Activity inhibitor.

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

ZINC08790006 is an novel inhibitor of SIRT1.

ZINC08792229 is a novel inhibitor of SIRT1.

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

Nicotinamide riboside malate is an orally active NAD+ precursor that elevates NAD+ levels and stimulates the activity of SIRT1 and SIRT3. Functioning as a vitamin B3 (niacin) source, it augments oxidative metabolism and provides protection against metabolic abnormalities induced by a high-fat diet. Additionally, Nicotinamide riboside malate mitigates cognitive decline in a genetically modified mouse model of Alzheimer's disease.

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 .

Cipepofol (HSK3486) is a GABAA receptor agonist with sedative properties and protective effects in a variety of cardiovascular diseases.Cipepofol activates the Sirtuin1 (Sirt1)/Nrf2 pathway and induces apoptosis in cardiomyocytes, and can be used to study myocardial infarction, myocardial ischemia/reperfusion injury, and octopus pot syndrome.

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].

Sulindac (Sulindac sulfoxide) is a sulfinylindene derivative prodrug with potential antineoplastic activity. Converted in vivo to an active metabolite, sulindac, a nonsteroidal anti-inflammatory drug (NSAID), blocks cyclic guanosine monophosphate-phosphodiesterase (cGMP-PDE), an enzyme that inhibits the normal apoptosis signal pathway; this inhibition permits the apoptotic signal pathway to proceed unopposed, resulting in apoptotic cell death.

Nicotinamide riboside chloride, also known as NR and SRT647, is a pyridine-nucleoside form of vitamin B3 that functions as a precursor to nicotinamide adenine dinucleotide or NAD+.

SRT 2104 (GSK2245840) is a selective and brain-permeable SIRT1 activator.

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].

SRT 2183 is a selective activator of Sirtuin-1 (SIRT1, EC1.5 : 0.36 μM).