Darapladib

A potent Lp-PLA2 inhibitor with IC50 of 0.25 nM; shows an enhanced in vitro and in vivo profile versus SB-435495.Atherosclerosis Phase 3 Discontinued (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) . (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. 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.

356057-34-6

SB-480848 | SB480848 | SB 480848

>98% (HPLC)

10 mM in DMSO

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

C36H38F4N4O2S

666.7711

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.