Ganoderic acid D, a highly oxygenated tetracyclic triterpenoid, is the major active component of Ganoderma lucidum. Ganoderic acid D upregulates the protein expression of SIRT3 and induces the deacetylated cyclophilin D (CypD) by SIRT3. Ganoderic acid D inhibits the energy reprogramming of colon cancer cells including glucose uptake, lactate production, pyruvate and acetyl-coenzyme production in colon cancer cells[1]. Ganoderic acid D can inhibit the growth of numerous cancer cell lines and it inhibits HeLa human cervical carcinoma cells with an IC50 of 17.3 mM[2].
SIRT7 inhibitor 97491, a potent SIRT7 inhibitor with an IC50 of 325 nM, reduces deacetylase activity of SIRT7 in a dose-dependent manner. SIRT7 inhibitor 97491 prevents tumor progression by increasing p53 stability through acetylation at K373/382. SIRT7 inhibitor 97491 promotes apoptosis through caspase pathway.[1].
SIRT2-IN-8 is a potent SIRT2 inhibitor. SIRT2-IN-8 can be used for Huntington’s and Parkinson’s diseases research[1].
Decapeptide-12, a small oligopeptide, is a tyrosinase inhibitor that interacts with C-terminal residue of tyrosinase (Kd: 61.1 μM). Decapeptide-12 is a competitive inhibitor of mushroom tyrosinase (IC50: 40 µM). Decapeptide-12 also increases transcription of SIRT. Decapeptide-12 reduces melanin content in melanocytes. Decapeptide-12 is used for the research of melanogenesis, senescence, inflammation [1][2][3].
Nicotinamide is a form of vitamin B3 that plays essential roles in cell physiology through facilitating NAD+ redox homeostasis and providing NAD+ as a substrate to a class of enzymes that catalyze non-redox reactions. Nicotinamide is an inhibitor of SIRT1.
A novel potent, selective Sirt2 inhibitor with IC50 of 0.118 uM; displays no inhibitory activity against Sirt1 and Sirt 3 (IC50>100 uM).
Sirt2-IN-1 (Compound 9) is a sirtuin 2 (Sirt2) inhibitor with an IC50 of 163 nM[1].
HSP70/SIRT2-IN-2 (Compounds 1a) is a dual inhibitor for SIRT2 and HSP70, with IC50 of 45.1±5.0 μM for SIRT2. HSP70/SIRT2-IN-2 has antitumor activity[1].
SPC-180002 is a SIRT1/3 dual inhibitor, with IC50 values of 1.13 and 5.41 μM, respectively. SPC-180002 disturbs redox homeostasis via ROS generation, which leads to an increase in both p21 protein stability and mitochondrial dysfunction. SPC-180002 strongly inhibits cell cycle progression and cancer cell growth. SPC-180002 activates the Nrf2 signaling pathway[1].
SIRT2-IN-9 (compound 12) is a selective inhibitor of SRIT2 with an IC50 value of 1.3 μM. SIRT2-IN-9 inhibits proliferative activity of MCF-7 breast cancer cells. SIRT2-IN-9 can be used for the research of cancer[1].
MDL-811, an allosteric SIRT6 activator, significantly activates SIRT6 histone H3 deacetylation (H3K9Ac, H3K18Ac, and H3K56Ac). MDL-811 could be used in the study of colorectal cancer[1].
SRT 2104 is a brain-permeable activator of SIRT1, used for the research of type 2 diabetes mellitus and Huntington's disease.
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[1].
MIND4-19 is a potent SIRT2 inhibitor with an IC50 value of 7.0 μM. MIND4-19 can be used for researching Huntington's disease[1].
UBCS039 is the first synthetic, specific Sirtuin 6 (SIRT6) activator, inducing autophagy in human tumor cells, with an EC50 of 38 μM[1].
7-Chloro-4-(piperazin-1-yl)quinolone is an important scaffold in medicinal chemistry. 7-Chloro-4-(piperazin-1-yl)quinolone is a potent sirtuin inhibitor and also inhibits the serotonin uptake (IC50 of 50 μM). 7-Chloro-4-(piperazin-1-yl)quinolone exhibits antimalarial activity on D10 and K1 strains of P. falciparum with IC50s of 1.18 μM and 0.97 μM, respectively[1].
SIRT6 activator 12q is potent, selective and orally active SIRT6 activator with IC50 values of 171.20, >200, >200, >200, 0.58 µM for SIRT1, SIRT2, SIRT3, SIRT5, SIRT6, respectively. SIRT6 activator 12q inhibits cell growth and migration. SIRT6 activator 12q induces Apoptosis and cell cycle arrest at G2 phase. SIRT6 activator 12q shows anticancer activity[1].
Sirtuin modulator 2 (Compound 132) is a sirtuin modulator with an ED50 equal or less than 50 μM[1].
Tenovin-1 is an inhibitor of sirtuin 1 and sirtuin 2, an activator of p53 and may have potential in the management of cancer.
SIRT1-IN-3 (compound 3j) is a potent and selective SIRT1 inhibitor, with an IC50 of 4.2 μM[1].
YK-3-237, a SIRT1 activator, targets mutant p53. YK-3-237 inhibits the proliferation of triple-negative breast cancer cells[1].
SIRT6-IN-2 (Compound 5) is a selective 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[1].
E1231 (E-1231) is a small molecule SIRT1 activator with EC50 of 0.83 uM, interactes with recombinant human SIRT1 protein and deacetylated liver X receptor-alpha (LXRα); increases ATP-binding cassette transporter A1 (ABCA1) expression in RAW 264.7 cells dependent on SIRT1 and LXRα, promotes cholesterol efflux and inhibited lipid accumulation in RAW 264.7 cells via SIRT1 and ABCA1; decreases total cholesterol and triglyceride levels in both serum and the liver in golden hamster hyperlipidemia models.
MDL-800 is an activator of SIRT6 deacetylation, with an EC50 value of 10.3 µM[1].
YM-08 (Compounds 7a) is a brain-penetrant inhibitors of SIRT2,with the IC50 of 19.9 μM. YM-08 also is inhibitor of Hsp70[1].
MDL-801 is an activator of SIRT6 deacetylation, with an EC50 value of 5.7 µM[1].
JGB1741 (ILS-JGB-1741) is a potent and specific SIRT1 activity inhibitor with an IC50 of ∼15 μM. JGB1741 is a weak SIRT2 and SIRT3 inhibitor with an all IC50>100 μM. JGB1741 increases the acetylated p53 levels leading to p53-mediated apoptosis with modulation of Bax/Bcl2 ratio, cytochrome c release and PARP cleavage. JGB1741 has the potential for breast cancer research[1].
Ophiopogonin D', isolated from the tubers of Ophiopogon japonicus, is a rare naturally occurring C29 steroidal glycoside. Ophiopogonin D' shows cytotoxic activity against two human tumor cell lines MG-63 and SNU387 with IC50s of 3.09 μM and 3.63 μM, respectively[1]. Ophiopogonin D' activates SIRT1 in a dose-dependent manner[2].
Thiomyristoyl is a potent and specific SIRT2 inhibitor with an IC50 of 28 nM.