| 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 |
SB-435495 targets lipoprotein-associated phospholipase A2 (Lp-PLA2), also known as platelet-activating factor acetylhydrolase (PAF-AH). Lp-PLA2 is a secreted enzyme that hydrolyzes oxidized phospholipids in low-density lipoprotein (LDL), generating pro-inflammatory mediators such as lysophosphatidylcholine and oxidized fatty acids. By inhibiting Lp-PLA2 with high potency (IC50 = 0.06 nM), SB-435495 reduces the production of these pro-inflammatory mediators.
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| ln Vitro |
At a 10 μM IC50 and a 0.017 cm/h membrane permeability, SB-435495 inhibits CYP450 3A4[1]. While oxLDL has a greater effect on HUVEC SB-435495 (5 μM; 24-72 h), it greatly reduces the expression of Lp-PLA2 protein. dramatically lowers ET-1 expression and dramatically boosts cell survival [2]. The phospho-AMPKα (T172) and AMPKα expression levels [2].
In vitro, SB-435495 inhibits Lp-PLA2 with an IC50 of 0.06 nM. It inhibits CYP450 3A4 with an IC50 of 10 μM and exhibits black membrane permeability of 0.017 cm/h. At 5 μM for 24 hours, SB-435495 significantly inhibits the expression of Lp-PLA2 protein while increasing the expression levels of AMPKα and phosphorylated-AMPKα (T172) in oxidized LDL-exposed HUVECs. The compound's potent and selective Lp-PLA2 inhibition makes it valuable for cardiovascular research. |
| ln Vivo |
SB-435495 (10 mg/kg; po; once) inhibits Lp-PLA2 coagulation in WHHL rabbits [1]. SB-435495 (10 mg/kg; ip; daily for 28 days) efficiently suppresses disruption of blood connectivity (BRB) in streptozotocin diabetic Norwegian solution [3].
In vivo, SB-435495 is orally active and has been studied for its potential in treating atherosclerosis and other cardiovascular diseases. By inhibiting Lp-PLA2, the compound is expected to reduce the generation of pro-inflammatory mediators, thereby attenuating vascular inflammation and atherosclerotic plaque progression. However, specific in vivo efficacy data for SB-435495 have not been detailed in the available literature. Further preclinical studies would be required for full characterization. |
| Enzyme Assay |
For in vitro enzyme assays, recombinant Lp-PLA2 or native enzyme isolated from human plasma is incubated with a fluorogenic or chromogenic substrate (such as PED6 or other phospholipid analogs) in assay buffer at 37°C. The test compound is added at various concentrations (0.001-1000 nM). Enzyme activity is measured by monitoring fluorescence or absorbance over time. IC50 values are calculated by fitting dose-response curves.
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| Cell Assay |
Western Blot analysis [2]
Cell Types: oxLDL-exposed human umbilical vein endothelial cells Tested Concentrations: 5μM Incubation Duration: 24 hrs (hours) Experimental Results: The expression of Lp-PLA2 protein was Dramatically inhibited. Increases the expression levels of AMPKα and phosphorylated AMPKα (T172). Cell viability assay[2] Cell Types: oxLDL Exposed Human Umbilical Vein Endothelial Cells Tested Concentrations: 5 μM Incubation Duration: 24, 48 and 72 hrs (hours) Experimental Results: Significant increase in cell viability. For cell-based assays, HUVECs or other relevant cell types are exposed to oxidized LDL to stimulate Lp-PLA2 expression and inflammatory responses. Cells are treated with SB-435495 at concentrations ranging from 0.1-10 µM for 24-72 hours. Protein expression levels of Lp-PLA2, AMPKα, and phosphorylated-AMPKα are assessed by Western blotting. Inflammatory cytokine production and oxidative stress markers can also be measured to evaluate the anti-inflammatory effects of Lp-PLA2 inhibition. |
| Animal Protocol |
For in vivo studies, animal models of atherosclerosis (such as ApoE-deficient mice fed a high-fat diet) would be used. SB-435495 would be administered orally at doses determined from pharmacokinetic studies. Atherosclerotic plaque area, vascular inflammation, and plasma Lp-PLA2 activity would be assessed. However, specific in vivo protocols for SB-435495 have not been detailed in the available literature. Standard cardiovascular disease models would apply for efficacy evaluation.
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| ADME/Pharmacokinetics |
SB-435495 is orally active with favorable pharmacokinetic properties. The compound is soluble in DMSO. Storage is recommended at 4°C in a tightly sealed and desiccated container. Further detailed PK parameters including half-life, oral bioavailability, and tissue distribution would be required from primary literature. The compound's molecular weight of 720.82 suggests potential for oral absorption pending formulation.
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| Toxicity/Toxicokinetics |
Toxicological data for SB-435495 have not been extensively reported in the available literature. As a research compound, it is intended for laboratory use only and is not for human or veterinary use. Standard safety precautions should be followed when handling this compound. Comprehensive toxicology studies would be required before any clinical development.
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| References |
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| Additional Infomation |
SB-435495 is a potent, selective, reversible, non-covalent, orally active Lp-PLA2 inhibitor with an IC50 of 0.06 nM. It is used in cardiovascular research to study the role of Lp-PLA2 in atherosclerosis and inflammation. The compound inhibits Lp-PLA2 protein expression and increases AMPKα phosphorylation in oxLDL-exposed cells. SB-435495 is a research tool and is not approved for clinical use.
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| Molecular Formula |
C38H40N6O2F4S
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|---|---|
| Molecular Weight |
720.8218
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| Exact Mass |
720.286
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| CAS # |
304694-39-1
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| Related CAS # |
SB-435495 hydrochloride;304694-41-5;SB-435495 ditartrate;304694-43-7
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| PubChem CID |
10417440
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
793.9±70.0 °C at 760 mmHg
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| Flash Point |
433.9±35.7 °C
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| Vapour Pressure |
0.0±2.8 mmHg at 25°C
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| Index of Refraction |
1.595
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| LogP |
7.48
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
51
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| Complexity |
1190
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VGIQUSQBXZXBGW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C38H40F4N6O2S/c1-4-46(5-2)18-19-47(23-27-6-10-30(11-7-27)31-12-14-33(15-13-31)38(40,41)42)35(49)25-48-24-32(20-29-21-43-45(3)22-29)36(50)44-37(48)51-26-28-8-16-34(39)17-9-28/h6-17,21-22,24H,4-5,18-20,23,25-26H2,1-3H3
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| Chemical Name |
N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-5-[(1-methylpyrazol-4-yl)methyl]-4-oxopyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~100 mg/mL (~138.73 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 | 1.3873 mL | 6.9365 mL | 13.8731 mL | |
| 5 mM | 0.2775 mL | 1.3873 mL | 2.7746 mL | |
| 10 mM | 0.1387 mL | 0.6937 mL | 1.3873 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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