Figure 1.

A, structures of inflammasome inducer BAA485 and BAA473. Structure–activity relationship studies revealed that moving the ketone from the 12-oxo position of the weak inflammasome inducer BAA485 to the 11-oxo position of BAA473 as well as adding the methyl pentanoate group results in a more potent inflammasome activity. B, BAA485 induces secretion of IL-18 in PBMCs. PBMCs were primed with 0.1 ng/ml LPS overnight. Following treatment with BAA485 (4-((3R,5R,10S,13R,17R)-3-hydroxy-10,13-dimethyl-12-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid) or BAA473 (methyl 4-((3R,5R,10S,12S,13R,17R)-3,12-dihydroxy-10,13-dimethyl-11-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate) for 16 h, IL-18 secretion was measured by AlphaLISA. Data presented are mean ± S.E. (error bars) (n = 3). *, p value <0.004 versus vehicle (paired t test).