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Purity: ≥98%
Sirtinol is a cell-permeable and specific inhibitor of the sirtuin deacetylase 1/2 (SIRT1/2) with potential anticancer and anti-inflammatory activity. It inhibits SIRT1/2 with IC50s of 131 μM and 38 μM in cell-free assays, respectively. It attenuates pro-inflammatory cytokine production and protects against hepatic injury following trauma-hemorrhage in male Sprague-Dawley rats. Sirtinol also inhibits the growth of MCF-7 cells in a concentration- and time-dependent manner.
| Targets |
Class III histone deacetylases (Sirtuins), primarily SIRT1 (IC50 = 26 μM) and SIRT2 (IC50 = 19 μM), using a fluorogenic peptide substrate. It showed no significant inhibition of class I/II HDACs (HDAC1, HDAC2, HDAC3) or SIRT3–SIRT7 (IC50 > 100 μM) [3]
- Neutrophil elastase (NE): Sirtinol inhibited NE activity with an IC50 of 12 μM, independent of Sirtuin inhibition [4] |
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| ln Vitro |
Sirtinol decreases the proliferation of MCF-7 cells in a concentration- and time-dependent way. After 24 and 48 hours of therapy, the IC50 values of sirtinol were 48.6 μM and 43.5 μM, respectively. Sirtinol dramatically lowers SIRT1 expression and increases acetylated p53 levels [1]. Sirtinol attenuates the proliferation and causes apoptosis of non-small cell lung cancer (NSCLC) H1299 cells, and leads to a large increase in the levels of FoxO3a, a pro-apoptotic transcription factor targeted by Sirt1 [2].
In MCF-7 human breast cancer cells, Sirtinol (25 μM, 50 μM) treatment for 48 hours dose-dependently reduced cell viability (by 35% at 25 μM, 65% at 50 μM) via MTT assay. Flow cytometry showed apoptotic cells increased from 5% (vehicle) to 28% (25 μM) and 52% (50 μM), with Western blot revealing elevated cleaved caspase-3/9 and LC3-II (autophagy marker, 3.0-fold increase at 50 μM) [1] - In A549 and H1299 human lung cancer cells, Sirtinol (10 μM–50 μM) inhibited proliferation with IC50 values of 35 μM (A549) and 40 μM (H1299) after 72 hours. Western blot showed reduced p-Akt (45% reduction at 40 μM), β-catenin (50% reduction), and increased Foxo3a (2.0-fold) and Bim (apoptosis marker, 2.5-fold) in A549 cells [2] - In recombinant human SIRT1/SIRT2 assays, Sirtinol (1 μM–100 μM) inhibited enzyme activity with IC50 = 26 μM (SIRT1) and IC50 = 19 μM (SIRT2), with no effect on SIRT3 (IC50 > 100 μM) [3] - In human neutrophils, Sirtinol (5 μM–20 μM) inhibited LPS-induced NE activity (IC50 = 12 μM) and reduced reactive oxygen species (ROS) production (by 40% at 20 μM) via DCFH-DA staining. qRT-PCR showed downregulated TNF-α (55% reduction) and IL-6 (60% reduction) mRNA at 20 μM [4] |
| ln Vivo |
Sirtinol has anti-inflammatory properties by directly inhibiting HNE activity and reducing HNE-induced and LPS-mediated tissue or organ damage [3].
In C57BL/6 mice with LPS-induced acute lung injury (ALI), intraperitoneal injection of Sirtinol (50 mg/kg, 100 mg/kg, once daily for 3 days) dose-dependently reduced lung injury. Lung myeloperoxidase (MPO) activity (a neutrophil marker) decreased by 45% (50 mg/kg) and 65% (100 mg/kg). Serum TNF-α/IL-6 levels were reduced by 50%/55% (100 mg/kg), and lung wet/dry weight ratio (edema marker) decreased from 5.2 (vehicle) to 3.8 (100 mg/kg) [4] |
| Enzyme Assay |
SIRT1/SIRT2 Inhibition Assay: Recombinant human SIRT1/SIRT2 proteins were incubated with a fluorogenic acetylated peptide substrate (Ac-RHKK(Ac)-AMC for SIRT1; Ac-KK(Ac)-AMC for SIRT2) and NAD⁺ (200 μM) in assay buffer (50 mM Tris-HCl pH 8.0, 1 mM DTT). Serial dilutions of Sirtinol (1 μM–100 μM) were added, and the mixture was incubated at 37°C for 60 minutes. A developer solution (containing a deacetylation-specific protease) was added, and fluorescence intensity (excitation 360 nm, emission 460 nm) was measured. IC50 values were calculated via four-parameter logistic regression [3]
- Neutrophil Elastase (NE) Activity Assay: Purified human NE was incubated with a chromogenic substrate (N-succinyl-Ala-Ala-Ala-p-nitroanilide) and serial dilutions of Sirtinol (1 μM–50 μM) in reaction buffer (50 mM Tris-HCl pH 8.0, 0.5 M NaCl). The mixture was incubated at 37°C for 30 minutes, and absorbance at 405 nm (p-nitroaniline release) was measured. IC50 for NE inhibition was calculated [4] |
| Cell Assay |
MCF-7 Breast Cancer Cell Assay: MCF-7 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Sirtinol (10 μM–50 μM) for 48 hours. Cell viability was measured via MTT assay. For apoptosis, cells were stained with Annexin V-FITC/PI and analyzed by flow cytometry. For Western blot, cells were lysed, proteins separated by SDS-PAGE, and probed with anti-cleaved caspase-3/9, anti-LC3-II, and anti-GAPDH antibodies [1]
- Lung Cancer Cell Assay: A549/H1299 cells were seeded in 96-well plates (4×10³ cells/well) and treated with Sirtinol (10 μM–50 μM) for 72 hours. IC50 was calculated via MTT assay. For pathway analysis, A549 cells were treated with 40 μM Sirtinol for 24 hours; Western blot detected p-Akt, β-catenin, Foxo3a, and Bim [2] - Neutrophil Function Assay: Human neutrophils were isolated and pre-treated with Sirtinol (5 μM–20 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 4 hours. ROS levels were measured via DCFH-DA staining (fluorescence intensity at 488/525 nm). NE activity in cell supernatants was measured via chromogenic assay, and TNF-α/IL-6 mRNA was quantified via qRT-PCR [4] |
| Animal Protocol |
Dissolved in DMSO, and diluted in saline; 1 mg/kg; i.v. injection Male Sprague-Dawley rats subjected to trauma-hemorrhage
LPS-Induced Acute Lung Injury (ALI) Mouse Model: Female C57BL/6 mice (8–10 weeks old) were randomized into 3 groups (n=6/group): vehicle (saline), Sirtinol 50 mg/kg, 100 mg/kg. ALI was induced by intratracheal instillation of LPS (5 mg/kg). Sirtinol was dissolved in saline and administered via intraperitoneal injection once daily for 3 days (starting 1 hour after LPS). On day 4, mice were euthanized: lung tissue was collected for MPO activity and wet/dry weight ratio; serum was collected for TNF-α/IL-6 quantification via ELISA [4] |
| Toxicity/Toxicokinetics |
In MCF-7/A549 cells, Sirtinol (at concentrations up to 100 μM) showed no significant toxicity to normal human mammary epithelial cells (HMEC) or bronchial epithelial cells (BEAS-2B) (cell viability > 80% at 50 μM concentration) [1][2] In ALI mice, Sirtinol (100 mg/kg, for 3 consecutive days) did not cause significant changes in body weight, serum ALT/AST (liver function), or creatinine (kidney function). No additional tissue damage was observed in lung/liver/kidney histology [4]
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| References |
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| Additional Infomation |
Sirtinol is a benzamide formed by the condensation of the carboxyl group of 2-{[(2-hydroxy-1-naphthyl)methylene]amino}benzoic acid with the amino group of 1-phenylethylamine. It possesses anti-inflammatory, EC 3.5.1.98 inhibitory, and Sir2 inhibitory activities. It belongs to the benzamide, aldehyde-imine, and naphthol classes of compounds. Functionally, it is related to anthranilic acid. Sirtinol is a first-generation selective class III HDAC (SIRT1/SIRT2) inhibitor developed to investigate Sirtuin-mediated biological processes (e.g., cell survival, metabolism) and to evaluate its anticancer/anti-inflammatory potential [3]. In cancer, Sirtinol exerts its antitumor effect by inhibiting SIRT1/SIRT2, leading to the accumulation of acetylated p53/Foxo3a, thereby triggering apoptosis and autophagic cell death [1][2]. In acute lung injury, Sirtinol alleviates inflammation through a dual mechanism: inhibiting neutrophil elastase (NE) activity and reducing the production of pro-inflammatory cytokines (TNF-α/IL-6), and this effect is independent of Sirtuin inhibition [4].
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| Molecular Formula |
C26H22N2O2
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| Molecular Weight |
394.47
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| Exact Mass |
394.168
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| CAS # |
410536-97-9
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| Related CAS # |
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| PubChem CID |
2827646
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
659.2±50.0 °C at 760 mmHg
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| Melting Point |
119-120℃
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| Flash Point |
352.5±30.1 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.623
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| LogP |
6.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
586
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UXJFDYIHRJGPFS-WPWMEQJKSA-N
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| InChi Code |
InChI=1S/C26H22N2O2/c1-18(19-9-3-2-4-10-19)28-26(30)22-13-7-8-14-24(22)27-17-23-21-12-6-5-11-20(21)15-16-25(23)29/h2-18,29H,1H3,(H,28,30)/b27-17+
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| Chemical Name |
2-[[(2-Hydroxy-1-naphthalenyl)methylene]amino]- N -(1-phenylethyl)benzamide
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| Synonyms |
Sirtinol
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O:0.4 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5350 mL | 12.6752 mL | 25.3505 mL | |
| 5 mM | 0.5070 mL | 2.5350 mL | 5.0701 mL | |
| 10 mM | 0.2535 mL | 1.2675 mL | 2.5350 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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