| CAS NO: | 356057-34-6 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| Molecular Weight (MW) | 666.77 |
|---|---|
| Formula | C36H38F4N4O2S |
| 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 info | 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 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 |
| Synonyms | SB-480848; SB 480848; Darapladib; SB480848 |
| 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 Vivo | In 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 model | WHHL rabbits |
| Formulation & Dosage | Dissolved in 1% aq methylcellulose; 30 mg/kg; p.o. |
| References | Bioorg 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. |
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