SIRT1 Activator

Nicotinamide riboside Chloride, an orally active NAD⁺ precursor, increases NAD⁺ levels and activates SIRT1 and SIRT3. Nicotinamide riboside Chloride is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside Chloride reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease.

SRT 1720 is a selective activator of human SIRT1 with an EC_1.5 of 0.16 μM, and shows less potent activities for SIRT2 and SIRT3 with EC_1.5s of 37 μM and > 300 μM, respectively.

Gamma-glutamylcysteine (γ-Glu-Cys) is an orally active, blood-brain barrier permeable dipeptide. Gamma-glutamylcysteine activates AMPK, SIRT1, IL-4/STAT6, AC/cAMP/PI3K, IGF-1R/IRS1/PI3K, and Nrf2 signaling pathways; it inhibits NF-κB, JAK1/STAT1/3, MAPKs, cadmium-induced p38 MAPK, JNK, and PI3K/Akt signaling pathways. Gamma-glutamylcysteine regulates macrophage polarization, modulates the trafficking of CD36 and GLUT4, induces glutathione synthesis, improves metabolic dysfunction, reduces lipid deposition, ameliorates glucose homeostasis, inhibits apoptosis (Apoptosis), stabilizes mitochondria, suppresses lipid peroxidation, iron accumulation and ferroptosis (Ferroptosis), reduces ds-HMGB1 levels, reverses mechanical hyperalgesia, and alleviates hepatic lipid droplet formation. Gamma-glutamylcysteine is applicable to research related to inflammatory bowel disease, type 2 diabetes, cadmium-induced neurotoxicity, Alzheimer's disease, cerebral ischemia/reperfusion injury, neuropathy, and alcoholic liver disease.

Phoenixin-20 (PNX-20) is a neuropeptide that activates GPR173. Phoenixin-20 inhibits LPS-induced TLR-4/MyD88/NF-κB signaling, pro-inflammatory cytokines, adhesion molecules, MMPs, and cytotoxicity. Phoenixin-20 increases SIRT1 and inhibits NLRP3/ASC/caspase-1, oxidative stress, and IL-1β/IL-18. Phoenixin-20 alleviates ox-LDL-induced endothelial dysfunction, monocyte adhesion, adhesion molecules, cytokines, NADPH oxidase/NOX-4, and ROS. Phoenixin-20 promotes GPR173/STAT6-mediated anti-inflammatory polarization of microglia and neuroprotection. Phoenixin-20 can be used in research on dental pulp infection, pulmonary arterial hypertension, atherosclerosis, neuroinflammation, anxiety, and neurodegenerative diseases.

SRT 2104 is a first-in-class, highly selective and brain-permeable activator of the NAD⁺ dependent deacetylase Sirt1, increases Sirt1 protein, but shows no effect on Sirt1 mRNA. Used in the research of diabetes mellitus and Huntington’s disease.

Sweroside is an iridoid glycoside that targets multiple targets, including the Keap1/Nrf2 axis, NLRP3 inflammasome, SIRT1, NF-κB, AMPK/mTOR pathway, and caspase family. Sweroside promotes Nrf2 nuclear translocation by competitively binding to Keap1. Sweroside also inhibits oxidative stress and NLRP3-mediated pyroptosis by activating Nrf2, inhibits NF-κB inflammatory pathway by activating SIRT1, and promotes autophagy and induces caspase-dependent apoptosis via the AMPK/mTOR pathway. Sweroside has antioxidant, anti-inflammatory, anti-apoptotic, and lipid metabolism regulating activities, and can be used in the research of myocardial ischemia-reperfusion injury, leukemia, acute lung injury, non-alcoholic fatty liver disease, and other fields.

Agrimol B, a polyphenol, is an orally active and potent SIRT1 activator. Agrimol B shows anti-adipogenic and anticancer activity. Agrimol B shows antibacterial activity against plant pathogens. Agrimol B dramatically inhibits 3T3-L1 adipocyte differentiation by reducing PPARγ, C/EBPα, FAS, UCP-1, and apoE expression. The action of Agrimol B on the cancer cells is likely derived from its effect on c-MYC, SKP2 and p27.

SRT 1720 dihydrochloride is a selective and orally active activator of SIRT1 with an EC₅₀ of 0.10 μM, and shows less potent activities on SIRT2 and SIRT3.

SRT 1460, a potent Sirtuin-1 (SIRT1) activator with an EC_1.5 value of 2.9 μM, shows good selectivity for activation of SIRT1 versus SIRT2 and SIRT3 (EC1.5>300 μM), and is more potent than Resveratrol and the closest sirtuin homologues.

SRT 1720 monohydrochloride is a selective and orally active activator of SIRT1 with an EC₅₀ of 0.10 μM, and shows less potent activities on SIRT2 and SIRT3.

Scopolin is a coumarin isolated from Arabidopsis thaliana (Arabidopsis) roots. Scopolin attenuated hepatic steatosis through activation of SIRT1-mediated signaling cascades.

SRT 2183 is a selective Sirtuin-1 (SIRT1) activator with an EC_1.5 value of 0.36 μM. SRT 2183 induces growth arrest and apoptosis, concomitant with deacetylation of STAT3 and NF-κB, and reduction of c-Myc protein levels.

Palmitoyl tetrapeptide-20 (PTP20) is a biomimetic peptide agonist of α-MSH. Palmitoyl tetrapeptide-20 promotes hair pigmentation and delays hair graying by activating the MC1-R pathway (AC₅₀: 0.16 nM), enhancing catalase activity to reduce H₂O₂ accumulation, and upregulating SIRT1 activity. Palmitoyl tetrapeptide-20 can be used in research on preventing hair loss and improving hair graying.

Segetalin B, an orally active cyclopentapeptide found in Vaccaria segetalis, possesses estrogen-like activity. Segetalin B promotes mineralization of ovariectomized rat-derived bone marrow mesenchymal stem cells (BMSCs) in vitro and increases the level of osteocalcin, BMP-2, ALP, and SIRT1 activity. Segetalin B is promising for research of post-menopausal osteoporosis (PMOP).

Loliolide (Loliolid) is a β-carotene metabolite. Loliolide reduces caspase 3, 8, 9 expression, enhances PI3K, AKT, SIRT1, inhibits ROS, apoptosis, and blocks NF-κB p65 nuclear translocation. Loliolide protects mitochondria, reduces oxidative stress, and increases cell viability in neuroblastoma cells. Loliolide can be used for the research of UV-induced skin damage and Parkinson’s disease.

CAY10602 is a SIRT1 activator. CAY10602 dose-dependently suppresses the NF-κB-dependent induction of TNF-α by lipopolysaccharide in THP-1 cells.

Spinacetin is an orally active flavonoid glycoside found in Inula japonica, with antioxidant and anti-inflammatory activities. Spinacetin inhibits major inflammatory signaling pathways such as Syk, MAPK, and NF-κB, and reduces Ca²⁺-dependent release of allergic mediators. Spinacetin induces protective autophagy and enhances antioxidant defense by upregulating SIRT3/SIRT1/PGC-1α, activating AMPK, and inhibiting mTOR and NF-κB, thereby exerting anti-apoptotic, cardioprotective, bladder-protective, and hepatoprotective effects. Spinacetin alleviates Doxorubicin (HY-15142A)-induced cardiotoxicity and reduces Cyclophosphamide (HY-17420)-induced hemorrhagic cystitis. Spinacetin can be used in research on allergic reactions, cardiotoxicity, cystitis, and cadmium-aggravated hepatic ischemia.

8-Prenylnaringenin is an orally active prenyl flavonoid. 8-Prenylnaringenin can be isolated from the hop spike Humulus lupulus. 8-Prenylnaringenin activates the PI3K/Akt pathway and the AMPK pathway, upregulates OXPHOS complexes (II, III, and V) and Sirt1, and reduces ROS production and SOD activity. 8-Prenylnaringenin improves muscle atrophy and obesity and inhibits angiogenesis. 8-Prenylnaringenin exhibits anticancer activity against glioblastoma and colon cancer. 8-Prenylnaringenin also has LH/FSH regulatory activity. 8-prenylnaringenin may be used in bone health research.

Lumbokinase attenuates myocardial ischemia-reperfusion (I-R) injury through the activation of Sirt1 signaling, and thus enhances autophagic flux and reduces I-R-induced oxidative damage, inflammation and apoptosis.

Nicotinamide riboside malate, an orally active NAD⁺ precursor, increases NAD⁺ levels and activates SIRT1 and SIRT3. Nicotinamide riboside malate is a source of vitamin B3 (niacin) and enhances oxidative metabolism, protection against high fat diet-induced metabolic abnormalities. Nicotinamide riboside malate reduces cognitive deterioration in a transgenic mouse model of Alzheimer’s disease.