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Darapladib(SB-480848)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Darapladib(SB-480848)图片
CAS NO:356057-34-6
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)666.77
FormulaC36H38F4N4O2S
CAS No.356057-34-6
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 100 mg/mL (150.0 mM)
Water: <1 mg/mL
Ethanol: 100 mg/mL (150.0 mM)
Other infoChemical 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
InChi Key: WDPFJWLDPVQCAJ-UHFFFAOYSA-N
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
SMILES Code: O=C(N(CCN(CC)CC)CC1=CC=C(C2=CC=C(C(F)(F)F)C=C2)C=C1)CN(C3=C4CCC3)C(SCC5=CC=C(F)C=C5)=NC4=O
SynonymsSB-480848; SB 480848; Darapladib; SB480848
实验参考方法
In Vitro

In vitro activity: During the copper catalysed oxidation of human LDL, Darapladib prevents the production of lyso-PtdCho with IC50 of 4 nM and subsequent monocyte chemotaxis with IC50 of 4 nM.


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


Cell Assay: 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).

In VivoIn the WHHL rabbits, Darapladib (30 mg/kg p.o.) exhibits excellent inhibition of Lp-PLA2 within the atherosclerotic plaque by 95%. Darapladib, as an inhibitor of Lp-PLA2, reduces development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic (DMHC) pigs. In DMHC pigs, darapladib reduces the amount of IgG-immunopositive material that leaked into the brain and also the density of Aβ42-containing neurons.
Animal modelWHHL rabbits
Formulation & DosageDissolved in 1% aq methylcellulose; 30 mg/kg; p.o.
ReferencesBioorg Med Chem Lett. 2003 Mar 24;13(6):1067-70; Nat Med. 2008 Oct;14(10):1059-66; J Alzheimers Dis. 2013;35(1):179-98.