Darapladib (Synonyms: SB-480848) |
| Catalog No.GC12361 |
A reversible inhibitor of Lp-PLA2
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 356057-34-6
Sample solution is provided at 25 µL, 10mM.
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Plaque rupture is responsible for the clinical events of ischemic death, myocardial infarction, acute coronary syndromes and ischemic strokes. Lipoprotein-associated phospholipase A2 (Lp-PLA2) seems to play a major role in the development of such high-risk lesions, in both the coronary and carotid arteries. Darapladib is a selective inhibitor of Lp-PLA2.
In vitro: Darapladib potently inhibited Lp-PLA2 with an IC50 of 270 pM. A lack of selectivity against other secretory PLA2s postulated to play a role in atherogenesis had been demonstrated. The percentage inhibition achieved when 1 μM darapladib was evaluated against human secretory PLA2s IIA, V and X, was 0, 0 and 8.7%, respectively [1].
In vivo: Inhibition of lp-PLA2 by darapladib led to attenuation of inflammation in vivo and decreased plaque formation in ApoE-deficient mice, suggesting an anti-atherogenic role during the progression of atherosclerosis [2].
Clinical trial: Darapladib produced sustained inhibition of plasma Lp-PLA2 activity in patients receiving intensive atorvastatin therapy. IL-6 and hs-CRP changes after 12 weeks of darapladib 160 mg suggested a possible reduction in inflammatory burden [3].
References:
[1] Bui QT, Wilensky RL. Darapladib. Expert Opin Investig Drugs. 2010;19(1):161-8.
[2] Wang WY, Zhang J, Wu WY, Li J, Ma YL, Chen WH, Yan H, Wang K, Xu WW, Shen JH, Wang YP. Inhibition of lipoprotein-associated phospholipase A2 ameliorates inflammation and decreases atherosclerotic plaque formation in ApoE-deficient mice. PLoS One. 2011;6(8):e23425.
[3] Mohler ER 3rd, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A; Darapladib Investigators. The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2008;51(17):1632-41.
Animal experiment: | Mice[2] Male homozygous LDLR-deficient mice (C57/Bl6 genetic background) are fed a high-fat diet consisting of 18% hydrogenated cocoa butter, 0.15% cholesterol, 7% casein, 7% sucrose, and 3% maltodextrin for 17 weeks, beginning at 6 weeks of age. Forty mice are divided into two groups (n=20 per group) randomly. One group receive Darapladib by gavage (50 mg/kg per day) once daily, while the other group receive the vehicle (saline). During the 6 weeks of treatment, all mice are housed in a room with a 12-h light/dark cycle and are allowed free access to a high-fat diet and water. |
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. | |
| Cas No. | 356057-34-6 | SDF | |
| Synonyms | SB-480848 | ||
| Chemical Name | N-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-1-yl]-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]acetamide | ||
| Canonical SMILES | CCN(CC)CCN(CC1=CC=C(C=C1)C2=CC=C(C=C2)C(F)(F)F)C(=O)CN3C4=C(CCC4)C(=O)N=C3SCC5=CC=C(C=C5)F | ||
| Formula | C36H38F4N4O2S | M.Wt | 666.77 |
| Solubility | ≥ 32.95 mg/mL in DMSO, ≥ 891 mg/mL in EtOH | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4998 mL | 7.4988 mL | 14.9977 mL |
| 5 mM | 0.3 mL | 1.4998 mL | 2.9995 mL |
| 10 mM | 0.15 mL | 0.7499 mL | 1.4998 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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