1. Metabolic Enzyme/Protease
  2. Phospholipase

Darapladib (Synonyms: SB-480848)

Cat. No.: HY-10521 Purity: 99.95%
Handling Instructions

Darapladib is a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) with IC50 of 0.25 nM.

For research use only. We do not sell to patients.
Darapladib Chemical Structure

Darapladib Chemical Structure

CAS No. : 356057-34-6

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 220 In-stock
5 mg USD 150 In-stock
10 mg USD 276 In-stock
50 mg USD 1188 In-stock
100 mg   Get quote  
200 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Darapladib is a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2) with IC50 of 0.25 nM.

IC50 & Target

IC50: 0.25 nM (Lp-PLA2)[1]

In Vitro

Mechanistic studies using steady state and transient kinetics indicate Darapladib (SB-480848) to be a freely reversible, non-covalently bound, inhibitor of rhLp-PLA2 with a Ki of 110 pM and an off-rate of 27 min. Potent inhibition of the enzyme in whole human plasma is confirmed (IC50=5±2 nM). Furthermore, the presence of Darapladib during the copper catalysed oxidation of human LDL prevents the production of lyso-PtdCho (IC50=4±3 nM) and subsequent monocyte chemotaxis (IC50=4±1 nM)[1].

In Vivo

Additional in vivo studies with Darapladib indicated an oral bioavailability of 11±2% in the fed rat. The oral bioavailability of Darapladib is 28±4% in the dog. Furthermore excellent inhibition of Lp-PLA2 within the atherosclerotic plaque is achieved for Darapladib, with 95±1% inhibition observed 2 h after an oral dose of 30 mg/kg to the WHHL rabbit[1]. Darapladib, a specific inhibitor of lipoprotein-associated phospholipase A2 (lp-PLA2), on inflammation and atherosclerotic formation in the low density lipoprotein receptor (LDLR)-deficient mice. the activity of serum lp-PLA2 is inhibited by more than 60% in LDLR-deficient mice after oral administration of 50 mg/kg once daily of Darapladib for 6 weeks. Darapladib significantly inhibits serum lp-PLA2 activity in LDLR-deficient mice[2].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 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
Please refer to the solubility information to select the appropriate solvent.
Animal Administration
[2]

Darapladib is prepared in saline (Mice)[2].

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. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

666.77

Formula

C₃₆H₃₈F₄N₄O₂S

CAS No.

356057-34-6

SMILES

FC1=CC=C(CSC(N(CC(N(CCN(CC)CC)CC2=CC=C(C3=CC=C(C(F)(F)F)C=C3)C=C2)=O)C4=C5CCC4)=NC5=O)C=C1

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Darapladib
Cat. No.:
HY-10521
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