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Purity: ≥98%
Salermide is a potent inhibitor of Sirt1/2 (Sirtuin 1/2) with a strong cancer-specific proapoptotic effect mediated by Sirt1. Class III histone deacetylases that are dependent on NAD+ (nicotinamide adenine dinucleotide-positive) include Sirt1 and Sirt2, which are involved in lifespan regulation. Since cancer is an age-related illness, focusing on sirtuins is becoming more and more popular as an antitumor tactic. Salermide is a reverse amide that significantly inhibits Sirt1 and Sirt2 in vitro. Salermide caused tumor-specific cell death in a variety of human cancer cell lines and was well tolerated by mice at concentrations up to 100 muM. Salermide's antitumor activity was mostly brought on by a significant induction of apoptosis. This suggested an in vivo mechanism of action via Sirt1 and was independent of global tubulin and K16H4 acetylation, ruling out a potential Sirt2-mediated apoptotic pathway. This is supported by the fact that cancer cells underwent apoptosis when Sirt1 but not Sirt2 was knocked down via RNA interference. Genetic p53 knockdowns demonstrated that Salermide's Sirt1-dependent proapoptotic effect is p53-independent, despite reports that p53 is a target of Sirt1. When combined, these findings point to the potential of salermide as an anticancer medication and provide light on the molecular pathway by which Sirt1 contributes to human carcinogenesis.
| Targets |
SIRT1; SIRT2
Salermide targets Sirtuin 1 (Sirt1) and Sirtuin 2 (Sirt2), which are NAD⁺-dependent class III histone deacetylases [1] |
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| ln Vitro |
In vitro activity: Salermide exhibits a dose-dependent inhibition against Sirt1 and Sirt2, which increases to 80% at 90 μM and 25 μM, respectively. In a variety of human cancer cell lines derived from leukemia (MOLT4, KG1A, K562), lymphoma (Raji), colon (SW480), and breast (MDA-MB-231), salermide can induce tumour-specific cell death. After being incubated at 100 μM Salermide alone, mitochondrial cytochrome was decreased and cytosolic activated caspase 3 was increased. Apoptosis can be induced by salermide alone via both intrinsic and extrinsic pathways. Compared to the previously reported class III HDAC inhibitors, salermide exhibited a number of antitumorigenic benefits. Firstly, it replicates the proapoptotic effect that the classical class I, II, and IV HDAC inhibitors showed on cancer samples, but it also has a cancer-specific proapoptotic effect[1]. Salermide exhibited a strong inhibitory effect on Sirt1 and Sirt2 in in vitro experiments [1] Salermide induced tumor-specific cell death in a wide range of human cancer cell lines, and its antitumor activity was mainly attributed to massive induction of apoptosis [1] The apoptotic effect of Salermide was independent of global tubulin and K16H4 acetylation, which excluded the possibility of a Sirt2-mediated apoptotic pathway and suggested that its in vitro mechanism of action might be related to Sirt1 [1] RNA interference (RNAi)-mediated knockdown of Sirt1 (but not Sirt2) induced apoptosis in cancer cells, which was consistent with the hypothesis that Salermide exerts its effect through Sirt1 [1] Genetic knockdown of p53 showed that the Sirt1-dependent proapoptotic effect of Salermide was p53-independent [1] Salermide exerted its apoptotic effect by reactivating proapoptotic genes that were epigenetically repressed exclusively in cancer cells by Sirt1 [1] |
| ln Vivo |
Salermide is well tolerated by mice at 100 μM concentrations. Sirt1 specifically mediates the mechanism of action of salermide in vivo. Salermide administered intraperitoneally to naked mice does not appear to be toxic[1].
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| Enzyme Assay |
The deacetylase activity of recombinant His-tagged human Sirt1 and Sirt2 was measured using the HDAC fluorescent activity assay (BIOMOL, Plymouth, PA, USA). The reactions lasted 60 minutes at 37 °C. The mean and standard deviation of four separate experiments are used to express the results.
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| Cell Assay |
Cell lines (SW480, MDA-MB-231, MOLT4, KG1A, K562 and Raji) are used in the study. Cell viability is determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. IC50 index is calculated using four Salermide concentrations (25, 50, 75 and 100 μM) for 24 h. The percentage of apoptotic cells is determined with the FACSCalibur apparatus[1].
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| Animal Protocol |
Mice: To determine whether salermide might have any negative in vivo effects. This is accomplished by injecting 100 μL of 100 μM salermide intraperitoneally into ten nude mice over a 34-day period. Throughout the research, an eye is kept on diet consumption, body weight gain, and changes in posture and behavior[1].
Salermide was tested for tolerance in mice, with administration at concentrations up to 100 μM; however, no specific details about the drug's dissolution formula, dosage form, administration frequency, or route (except for tolerance testing) were provided [1] |
| References | |
| Additional Infomation |
N-[3-[(2-oxo-1-naphthylmethylene)methylamino]phenyl]-2-phenylpropionamide belongs to the naphthalene class of compounds. Salermide, chemically named N-{3-[(2-hydroxy-naphthyl-1-ylmethylene)-amino]phenyl}-2-phenylpropionamide, belongs to the trans-amide class of compounds [1]. Sirt1 and Sirt2 are involved in regulating lifespan, and cancer is an age-related disease; therefore, targeting Sirtuins has become a promising anti-tumor strategy [1]. The results of this study indicate that Salermide has the potential as an anti-cancer drug and provide evidence for the molecular mechanism by which Sirt1 participates in human tumorigenesis [1].
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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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| Elemental Analysis |
C, 79.17; H, 5.62; N, 7.10; O, 8.11
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| CAS # |
1105698-15-4
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| Related CAS # |
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| PubChem CID |
135659046
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
666.7±50.0 °C at 760 mmHg
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| Flash Point |
357.0±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 |
5.4
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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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| SMILES |
O=C(NC1=CC=CC(/N=C/C2=C3C=CC=CC3=CC=C2O)=C1)C(C)C4=CC=CC=C4
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| InChi Key |
HQSSEGBEYORUBY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H22N2O2/c1-18(19-8-3-2-4-9-19)26(30)28-22-12-7-11-21(16-22)27-17-24-23-13-6-5-10-20(23)14-15-25(24)29/h2-18,29H,1H3,(H,28,30)
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| Chemical Name |
N-[3-[(2-hydroxynaphthalen-1-yl)methylideneamino]phenyl]-2-phenylpropanamide
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| Synonyms |
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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: ≥ 2.5 mg/mL (6.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (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.
Design and synthesis of Salermide.Oncogene.2009 Feb 12;28(6):781-91. |
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Sirt1 and Sirt2in vitroinhibition and cancer-specific cell death induction by Salermide.Oncogene.2009 Feb 12;28(6):781-91. |
Salermide induces dose-dependent apoptosis in cancer cells lines but not inin vitro-cultured fibroblasts.Oncogene.2009 Feb 12;28(6):781-91. |
In vivobiological effects of Salermide are not primarily mediated by Sirt2.Oncogene.2009 Feb 12;28(6):781-91. |
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In vivobiological effects of Salermide are primarily mediated by Sirt1.Oncogene.2009 Feb 12;28(6):781-91. |
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