SIRT1 Inhibitor

Nicotinamide is a form of vitamin B3 or niacin. Nicotinamide Hydrochloride inhibits SIRT2 activity (IC₅₀: 2 μM). Nicotinamide also inhibits SIRT1. Nicotinamide increases cellular NAD₊, ATP, ROS levels. Nicotinamide inhibits tumor growth and improves survival. Nicotinamide also has anti-HBV activity.

Suramin sodium salt (Suramin hexasodium salt) is a reversible and competitive protein-tyrosine phosphatases (PTPases) inhibitor. Suramin sodium salt is a potent inhibitor of sirtuins: SirT1 (IC₅₀=297 nM), SirT2 (IC₅₀=1.15 μM), and SirT5 (IC₅₀=22 μM). Suramin sodium salt is a competitive inhibitor of reverse transcriptase (DNA topoisomerase II: IC₅₀=5 μM). Suramin sodium salt is a potent SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitor. Suramin sodium salt efficiently inhibits IP5K and is an antiparasitic, anti-neoplastic and anti-angiogenic agent.

NH4-6 is a SIRT2 inhibitor with an IC₅₀ of 0.032 μM against SIRT2 and an IC₅₀ of 3 μM against SIRT1. NH4-6 inhibits the deacetylase activity of SIRT1. As a cytotoxic agent, NH4-6 reduces cancer cell viability, suppresses anchorage-independent growth of cancer cells, induces acetylation of α-tubulin, and promotes acetylation of p53. NH4-6 can be used in the research of breast cancer.

Sirt1/2-IN-5 is a SIRT1/SIRT2 inhibitor with human SIRT1 IC₅₀ 0.3 μM and human SIRT2 IC₅₀ values 1.2 μM and pIC₅₀ 5.82. Sirt1/2-IN-5 inhibits NAD⁺-dependent deacetylase activity of SIRT1 and SIRT2. Sirt1/2-IN-5 can be used for the research of cancer, neurodegenerative disease.

AGK2 is a selective SIRT2 inhibitor with an IC₅₀ of 3.5 μM. AGK2 inhibits SIRT1 and SIRT3 with IC₅₀s of 30 and 91 μM, respectively.

OSS_128167 is a potent selective sirtuin 6 (SIRT6) inhibitor with IC₅₀s of 89 μM, 1578 μM and 751 μM for SIRT6, SIRT1 and SIRT2, respectively. OSS_128167 has anti-HBV activity that inhibits HBV transcription and replication. OSS_128167 has anti-cancer, anti-inflammation and anti-viral effects.

Sirtinol is a sirtuin (SIRT) inhibitor, with IC₅₀s of 48 μM, 57.7 μM and 131 μM for ySir2, hSIRT2 and hSIRT2, respectively.

Tenovin-6, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 inhibits the protein deacetylase activities of purified human SIRT1, SIRT2, and SIRT3 with IC₅₀s of 21 μM, 10 μM, and 67 μM, respectively. Tenovin-6 also inhibits dihydroorotate dehydrogenase (DHODH).

Cambinol is a SIRT1 and SIRT2 inhibitor with IC₅₀ values of 56 μM and 59 μM, respectively. Cambinol is a potent brain penetrant neutral sphingomyelinase (N-SMase) inhibitor (exosome inhibitor).

Thiomyristoyl is a potent and specific SIRT2 inhibitor with an IC₅₀ of 28 nM.

2''-O-Galloylhyperin is an active natural compound with anti‑inflammatory, antioxidant, anti‑adipogenic, antifibrotic, and cytostatic activities. 2''-O-Galloylhyperin upregulates SIRT1/Nrf2 signaling, inhibits NF-κB and MAPK (ERK1/2, p38, JNK) phosphorylation, suppresses TSHR activation, reduces ROS accumulation, and enhances SOD and GSH-Px activities. 2''-O-Galloylhyperin protects against LPS-induced tissue injury, enhances survival, and inhibits adipogenesis and fibrosis. 2"-O-Galloylhyperin can be used for the research of sepsis, acute lung injury, and thyroid eye disease.

Inauhzin is a dual SirT1/IMPDH2 inhibitor, and acts as an activator p53, used in the research of cancer.

Salermide is an inhibitor of Sirt1 and Sirt2; can cause strong cancer-specific apoptotic cell death.

SIRT-IN-2 is a potent inhibitor of SIRT1/2/3, with IC₅₀s of 4, 4, 7 nM, respectively.

SIRT1-IN-1 is a selective SIRT1 inhibitor with an IC₅₀ of 0.205 μM. SIRT1-IN-1 inhibits SIRT2 with an IC₅₀ of 11.5 μM. SIRT1-IN-1, a indole, is a cytomegalovirus (CMV) inhibitors and has antiviral activity.

SIRT6-IN-2 (Compound 5) is a selective and competitive SIRT6 inhibitor (IC₅₀: 34 μM). SIRT6-IN-2 increases acetylation of H3K9 and increases glucose uptake in cultured cells. SIRT6-IN-2 also reduces T cell proliferation. SIRT6-IN-2 has immunosuppressive and chemosensitizing effects.

SIRT6-IN-6 (compound 6d) is a potent and selective SIRT6 inhibitor with an IC₅₀ of 4.93 μM and a K_i of ~10 μM. SIRT6-IN-6 shows selectivity against other members of the HDAC family (SIRT1-3 and HDAC1-11). SIRT6-IN-6 significantly increases the level of glucose transporter GLUT-1, thereby reducing blood glucose in a mouse model of type 2 diabetes. SIRT6-IN-6 can be used for type 2 diabetes research.

NSC 90469 (3,5-Diiodo-L-thyronine) is an orally active thyroid hormone derivative. NSC 90469 inhibits JNK phosphorylation and NF-κB acetylation, blocks SIRT1 protein expression, induces elevated PGC-1α levels, and stimulates COX activity. NSC 90469 enhances UCP1-mediated thermogenesis, increases hepatic Dio1 activity, inhibits TSH levels and hypothalamic-pituitary-thyroid axis function, enhances lipid metabolism, and regulates energy metabolism via the mitochondrial pathway. NSC 90469 prevents blood glucose reduction, reduces urinary albumin excretion, inhibits renal matrix expansion, decreases TGF-β1 expression, and reduces renal fibronectin and type Ⅳ collagen deposition. NSC 90469 also increases energy expenditure and prevents diet-induced overweight. NSC 90469 can be used in studies related to diabetic nephropathy, hypothyroidism, non-alcoholic fatty liver disease, and diet-induced obesity.

Schisanhenol (Schizanhenol), a lignan, is an orally active antioxidant. Schisanhenol reduces AChE activity, increases SIRT1 and PGC-1α expression, and decreases phosphorylated Tau (Ser 396) levels. Schisanhenol increases SOD and glutathione peroxidase activity, decreases malondialdehyde (MDA) content, and inhibits UGT2B7 activitY. Schisanhenol attenuates ox-LDL-induced apoptosis, intracellular reactive oxygen species generation, and cytotoxicity in endothelial cells. Schisanhenol inhibits LDL oxidation, brain mitochondrial and membrane peroxidative damage, and brain mitochondrial swelling and disintegration. Schisanhenol can be used for the research of Alzheimer’s disease, atherosclerosis, brain ischemia, and age-related brain deterioration.

Dihydrocoumarin 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.