Sirtuin Inhibitor

Et-29 (NRD167) is a selective SIRT5 inhibitor. Et-29 increases the levels of total protein succinylation and citrate synthase succinylation in cells. Et-29 reduces serum CTX-I levels and blocks Ferroptosis by downregulating the SIRT5/ACSL4/LPCAT3/ALOX15 axis and restoring antioxidant defense. Et-29 decreases bone resorption and improves trabecular bone mass and microarchitecture. Et-29 is applicable for research related to osteoporosis and hepatocellular carcinoma.

PDRN (Polydeoxyribonucleotide) is a deoxynucleotide polymer mainly derived from the sperm of rainbow trout or salmon. PDRN inhibits pro-inflammatory factors and promotes VEGF expression via the cAMP-PKA pathway by activating the adenosine A_2A receptor (A_2AR), thereby driving angiogenesis and collagen deposition in fibroblasts. Degradation products of PDRN provide DNA raw materials for proliferating cells through the salvage synthesis pathway, accelerating re-epithelialization. PDRN reduces melanin synthesis and cell apoptosis by upregulating ERK/AKT phosphorylation and inhibiting the activities of MITF and tyrosinase, and resists skin aging by attenuating nuclear autophagy and blocking the interaction between LC3-SIRT1. PDRN is mainly used for wound repair, post-aesthetic surgery recovery and anti-aging research.

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

Tenovin-1, a p53 activator, protects p53 from MDM2-mediated degradation. Tenovin-1 acts through inhibition of the protein-deacetylating activities of SirT1 and SirT2. Tenovin-1 is also a dihydroorotate dehydrogenase (DHODH) inhibitor.

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.

SIRT1 Human Pre-designed siRNA Set A contains three designed siRNAs for SIRT1 gene (Human), as well as a negative control, a positive control, and a FAM-labeled negative control.

Rencofilstat (CRV431) is an orally active pan-cyclophilin inhibitor with IC₅₀ values of 2.5 nM, 3.1 nM, 2.8 nM, 7.3 nM for Cyp A, CypB, Cyp D and Cyp G, respectively. Rencofilstat reduces fibrosis and tumor growth in models of chronic liver disease. Rencofilstat can be used for the study of nonalcoholic steatohepatitis (NASH), hepatocellular carcinoma and viral hepatitis-induced liver disease.

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).

SIRT-IN-3 is a potent SIRT inhibitor, with an IC₅₀ of 17 μM for SIRT1. SIRT-IN-3 shows about 4-fold and 14-fold selectivity for SIRT1 over SIRT2 and SIRT3, respectively (IC₅₀ of 74 μM and 235 μM for SIRT2 and SIRT3, respectively).

SIRT5 inhibitor 3 (compound 46) is a potent and competitive SIRT5 inhibitor with an IC₅₀ value of 5.9 μM. SIRT5 inhibitor 3 can inhibit SIRT5 desuccinylation. SIRT5 inhibitor 3 can be used for researching cancer and neurodegenerative diseases.

YZL-51N is a selective SIRT7 inhibitor with IC₅₀ value of 12.71 μM. YZL-51N disrupts SIRT7 enzyme activity by occupying the NAD⁺ binding pocket, thereby weakening DNA damage repair and inhibiting cancer cell survival. YZL-51N possesses anti-tumor activity and can be used in cancer research.

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.

JFD00244 is a sirtuin 2 (SIRT2) inhibitor, with anti-tumor effect. JFD00244 is also a Nsp-16 inhibitor against SARS-CoV-2.

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.

Tenovin-6 Hydrochloride, an analog of Tenovin-1 (HY-13423), is an activator of p53 transcriptional activity. Tenovin-6 Hydrochloride 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 Hydrochloride also inhibits dihydroorotate dehydrogenase (DHODH).