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Purity: ≥98%
Darapladib (formerly also known as SB-480848; SB 480848; SB480848), a substituted pyrimidone, is a novel, potent and reversible inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor with potential anti-inflammatory activity. It inhibits Lp-PLA2 with an IC50 of 0.25 nM. Darapladib is under development in Phase 3 clinical trials for the treatment of atherosclerosis.
| ln Vitro |
In C6 glioma cells and U251MG, darapladib (5 μM; 6, 12 h) can cause cell cycle arrest [2]. Glioma cell apoptosis is triggered by darapladib (5 μM; 3, 6 h) [2]. In glioma cells, darapladib (5 μM; 5, 15, 30, 60, and 90 min) can cause an increase in ERK1/2 protein phosphorylation [2].
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| ln Vivo |
In mice lacking LDLR, darapladib (50 mg/kg; po; once daily for 6 weeks) can considerably reduce serum Lp-PLA2 activity [3]. In mice, darapladib (50 mg/kg; po; once daily for 6 weeks) can lower the levels of IL-6 and hs-CRP in the serum [3].
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| Cell Assay |
Apoptosis Analysis[2]
Cell Types: C6 glioma cells and U251MG cells. Tested Concentrations: 5 μM Incubation Duration: 3, 6 h Experimental Results: Triggered cell apoptosis in glioma cells. Cell Cycle Analysis[2] Cell Types: C6 glioma cells and U251MG cells. Tested Concentrations: 5 μM Incubation Duration: 6, 12 h Experimental Results: Induced cell cycle arrest in glioma cells. Western Blot Analysis[2] Cell Types: C6 glioma cells and U251MG cells. Tested Concentrations: 5 μM Incubation Duration: 5, 15, 30, 60 and 90 min Experimental Results: Induced an increase in phosphorylation of ERK1/2 proteins, but decreased AKT phosphorylation in glioma cells. |
| Animal Protocol |
Animal/Disease Models: Male homozygous LDLR-deficient mice (C57/Bl6 genetic background)[3].
Doses: 50 mg/kg Route of Administration: Oral administration; one time/day for 6 weeks. Experimental Results: Dramatically inhibited activity of serum Lp-PLA2. |
| References |
[1]. Blackie JA, et al. The identification of clinical candidate SB-480848: a potent inhibitor of lipoprotein-associated phospholipase A2. Bioorg Med Chem Lett. 2003 Mar 24;13(6):1067-70.
[2]. Wang YJ, et al. The selective lipoprotein-associated phospholipase A2 inhibitor darapladib triggers irreversible actions on glioma cell apoptosis and mitochondrial dysfunction. Toxicol Appl Pharmacol. 2020 Sep 1;402:115133. [3]. Hu MM, et al. The inhibition of lipoprotein-associated phospholipase A2 exerts beneficial effects against atherosclerosis inLDLR-deficient mice. Acta Pharmacol Sin. 2011 Oct;32(10):1253-1258. [4]. Riley RF, et al. Darapladib, a reversible lipoprotein-associated phospholipase A2 inhibitor, for the oral treatment of atherosclerosis and coronary artery disease. IDrugs. 2009 Oct;12(10):648-55. |
| Molecular Formula |
C36H38F4N4O2S
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|---|---|
| Molecular Weight |
666.7711
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| CAS # |
356057-34-6
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| Related CAS # |
1389264-17-8 (Darapladib-impurity)
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| SMILES |
S(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])F)C1=NC(C2C([H])([H])C([H])([H])C([H])([H])C=2N1C([H])([H])C(N(C([H])([H])C1C([H])=C([H])C(C2C([H])=C([H])C(C(F)(F)F)=C([H])C=2[H])=C([H])C=1[H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])=O)=O
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| InChi Key |
WDPFJWLDPVQCAJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C36H38F4N4O2S/c1-3-42(4-2)20-21-43(22-25-8-12-27(13-9-25)28-14-16-29(17-15-28)36(38,39)40)33(45)23-44-32-7-5-6-31(32)34(46)41-35(44)47-24-26-10-18-30(37)19-11-26/h8-19H,3-7,20-24H2,1-2H3
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| Chemical Name |
N-[2-(diethylamino)ethyl]-2-[[(4-fluorophenyl)methyl]thio]-4,5,6,7-tetrahydro-4-oxo-N-[[4-(trifluoromethyl)[1,1-biphenyl]-4-yl]methyl]-1H-Cyclopentapyrimidine-1-acetamide
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| Synonyms |
SB-480848; SB 480848; Darapladib;SB480848
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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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4998 mL | 7.4988 mL | 14.9977 mL | |
| 5 mM | 0.3000 mL | 1.4998 mL | 2.9995 mL | |
| 10 mM | 0.1500 mL | 0.7499 mL | 1.4998 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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