Darapladib

Cas No.:	356057-34-6
Chemical Name:	SB-480848; SB480848; SB 480848
Synonyms:	SB-480848; SB480848; SB 480848
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
Formula:	C36H38F4N4O2S
M.Wt:	666.77
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

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