| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg | |||
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| Targets |
Target: SIRT5 (Sirtuin 5, an NAD+-dependent lysine deacylase). SIRT5 preferentially removes negatively charged acyl modifications (succinyl, malonyl, glutaryl) from lysine residues, regulating enzymes involved in fatty acid oxidation, ketogenesis, and the urea cycle. SIRT5 is upregulated in some cancers and contributes to metabolic reprogramming and resistance to oxidative stress. SIRT5 inhibitor 3 is a potent and selective SIRT5 inhibitor, with IC50 in the low micromolar range.
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| ln Vitro |
In vitro, SIRT5 inhibitor 3 potently inhibits SIRT5 deacylase activity in cell-free assays, with IC50 values reported in the low uM range (specific value not disclosed). It shows selectivity for SIRT5 over other sirtuins (SIRT1, SIRT2, SIRT3, SIRT6). In cellular assays, it increases succinylation and glutarylation levels of known SIRT5 substrates (e.g., carbamoyl phosphate synthetase 1, CPS1; pyruvate dehydrogenase, PDH). It may affect cellular metabolism and oxidative stress responses.
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| ln Vivo |
No in vivo efficacy data have been published specifically for SIRT5 inhibitor 3 in animal models. As a SIRT5 inhibitor, it is expected to have effects in mouse models of cancer (e.g., colorectal, liver, breast) where SIRT5 is overexpressed, as well as in metabolic diseases and ischemia-reperfusion injury. Detailed animal studies have not been reported.
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| Enzyme Assay |
For cell-free SIRT5 deacylase activity assays: recombinant SIRT5 protein (50-100 ng) is incubated with varying concentrations of SIRT5 inhibitor 3 (0-100 uM), NAD+ (1-2 mM), and a fluorogenic peptide substrate (e.g., Ac-Arg-His-Lys-Succinyl-Lys-AMC or Ac-Arg-His-Lys-Glutaryl-Lys-AMC) in assay buffer (50 mM Tris-HCl pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM MgCl2, 1 mg/mL BSA, 1 mM DTT) at 37degC for 30-60 min. The reaction is stopped by adding developer solution containing trypsin and nicotinamide, and fluorescence is measured at 360/460 nm. IC50 is calculated from dose-response curves. For selectivity, similar assays are performed with SIRT1, SIRT2, SIRT3, SIRT6.
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| Cell Assay |
For cell-based assays: cancer cell lines (e.g., HCT116, HepG2, MCF7) are seeded in 6-well plates and treated with SIRT5 inhibitor 3 (1-100 uM, 24-48 h). Cells are lysed, and protein lysates are analyzed by Western blot using antibodies against succinyl-lysine, glutaryl-lysine, and malonyl-lysine to assess global changes in acylation levels. Specific SIRT5 substrates (e.g., CPS1, PDH) are immunoprecipitated and analyzed for increased succinylation. Cell viability is measured by MTT assay. Metabolic assays (e.g., oxygen consumption rate, extracellular acidification rate) can be performed using Seahorse analyzer.
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| Animal Protocol |
For in vivo animal studies: potential protocol involves xenograft mouse models bearing SIRT5-overexpressing tumors (e.g., HCT116, HepG2). SIRT5 inhibitor 3 would be formulated in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline and administered intraperitoneally (10-50 mg/kg) daily for 2-3 weeks. Tumor volume would be measured. Tumor tissues would be harvested for analysis of succinylation/glutarylation levels, metabolic markers, and apoptosis. No published data are available.
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| ADME/Pharmacokinetics |
No PK data are available for SIRT5 inhibitor 3. For a small molecule SIRT5 inhibitor (MW ~400-500, LogP ~2-3), predicted PK in rodents after IP administration: moderate bioavailability, Tmax 0.5-1 h, plasma half-life 2-4 h. The compound is soluble in DMSO. In vivo formulation: 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline. Oral bioavailability is unknown.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for SIRT5 inhibitor 3. SIRT5 is involved in detoxification of reactive oxygen species and ammonia, so its inhibition may cause oxidative stress and hyperammonemia. However, SIRT5 knockout mice are viable and healthy, suggesting a safety window. The compound is for research use only and not for human consumption.
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| References | |
| Additional Infomation |
SIRT5 inhibitor 3 is a research compound not yet approved for clinical use. It is a valuable tool for studying the role of SIRT5 in metabolism, oxidative stress, cancer, and other diseases. It has potential applications in cancer research (metabolic reprogramming, resistance to therapy), metabolic disorders (obesity, diabetes, fatty liver disease), and neurodegenerative diseases. The compound is also used as a chemical probe to validate SIRT5 as a therapeutic target.
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| Molecular Formula |
C22H12FN3O4
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|---|---|
| Molecular Weight |
401.346788406372
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| Exact Mass |
401.081
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| CAS # |
2128651-12-5
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| PubChem CID |
137639138
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| Appearance |
Orange to red solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
787
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(O)(=O)C1=CC=C(C2=CC=C(/C=C(\C#N)/C(NC3=CC=C(C#N)C(F)=C3)=O)O2)C=C1
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| InChi Key |
ZXUUSUJEPKBBBB-CXUHLZMHSA-N
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| InChi Code |
InChI=1S/C22H12FN3O4/c23-19-10-17(6-5-15(19)11-24)26-21(27)16(12-25)9-18-7-8-20(30-18)13-1-3-14(4-2-13)22(28)29/h1-10H,(H,26,27)(H,28,29)/b16-9+
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| Chemical Name |
4-[5-[(E)-2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxoprop-1-enyl]furan-2-yl]benzoic acid
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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 |
| 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) |
DMSO : ~25 mg/mL (~62.29 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4916 mL | 12.4580 mL | 24.9159 mL | |
| 5 mM | 0.4983 mL | 2.4916 mL | 4.9832 mL | |
| 10 mM | 0.2492 mL | 1.2458 mL | 2.4916 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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