Physicochemical Properties
| Molecular Formula | C42H46F4N6O8S |
| Molecular Weight | 1021.00 |
| Exact Mass | 1020.319 |
| CAS # | 304694-43-7 |
| Related CAS # | SB-435495;304694-39-1;SB-435495 hydrochloride;304694-41-5 |
| PubChem CID | 168265969 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 8 |
| Hydrogen Bond Acceptor Count | 21 |
| Rotatable Bond Count | 21 |
| Heavy Atom Count | 71 |
| Complexity | 1330 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | CCN(CC)CCN(CC1=CC=C(C=C1)C2=CC=C(C=C2)C(F)(F)F)C(=O)CN3C=C(C(=O)N=C3SCC4=CC=C(C=C4)F)CC5=CN(N=C5)C.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O |
| InChi Key | BCBWEOPNBBMTKX-WBPXWQEISA-N |
| InChi Code | InChI=1S/C38H40F4N6O2S.2C4H6O6/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;2*5-1(3(7)8)2(6)4(9)10/h6-17,21-22,24H,4-5,18-20,23,25-26H2,1-3H3;2*1-2,5-6H,(H,7,8)(H,9,10)/t;2*1-,2-/m.11/s1 |
| 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;(2R,3R)-2,3-dihydroxybutanedioic acid |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | Lp-PLA2 0.06 nM (IC50) |
| ln Vitro | CYP450 3A4 is inhibited by SB-435495 ditartrate, which has an IC50 of 10 μM and a membrane permeability of 0.017 cm/h[1]. In HUVECs exposed to oxLDL, SB-435495 (5 μM; 24 h) ditartrate markedly reduced the expression of Lp-PLA2 protein while upregulating the expression levels of AMPKα and phospho-AMPKα (T172) [2]. In HUVECs exposed to oxLDL, SB-435495 (5 μM; 24-72 h) ditartrate dramatically reduced ET-1 expression, while also increasing cell survival and NO expression [2]. |
| ln Vivo | In WHHL rabbits, SB-435495 (10 mg/kg; po; once) ditartrate suppresses plasma Lp-PLA2[1]. In streptozotocin-diabetic brown Norway rats, SB-435495 (10 mg/kg; ip; daily for 28 days) ditartrate significantly suppresses blood-retinal barrier (BRB) disruption[3]. |
| Cell Assay |
Western Blot Analysis[2] Cell Types: oxLDL-exposed human umbilical vein endothelial cells Tested Concentrations: 5 μM Incubation Duration: 24 h Experimental Results: The expression of Lp-PLA2 protein was Dramatically inhibited. Increased 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 h Experimental Results: Dramatically increased cell viability. |
| Animal Protocol |
Animal/Disease Models: WHHL rabbit[1] Doses: 10 mg/kg Route of Administration: po (oral gavage) once Experimental Results: Inhibited plasma Lp-PLA2 in the WHHL rabbit. |
| References |
[1]. The discovery of SB-435495. A potent, orally active inhibitor of lipoprotein-associated phospholipase A(2) for evaluation in man. Bioorg Med Chem Lett. 2002 Sep 16;12(18):2603-6. [2]. AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis. Exp Ther Med. 2017 Apr;13(4):1622-1629. [3]. Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7213-8. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9794 mL | 4.8972 mL | 9.7943 mL | |
| 5 mM | 0.1959 mL | 0.9794 mL | 1.9589 mL | |
| 10 mM | 0.0979 mL | 0.4897 mL | 0.9794 mL |