GlaxoSmithKline is investigating a series of substituted pyrimidin-4-ones, including SB-435495, as reversible inhibitors of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) for the potential treatment of atherosclerosis [339220], [422380]. This series is being developed alongside a series of irreversible inhibitors such as SB-222657 and derivatives of SB-253514 [339220], [401355]. SB-435495 was discovered through the use of gene technology provided by Human Genome Sciences (HGS) [400047]. By October 2001, phase II trials of SB-435495 had been initiated [424613].