Figure 2.

COX-2 and inflammatory prostaglandin signaling pathways. (A) COX cascade mediates a variety of physiological and pathological events via its prostanoid products. In response to disparate stimuli, the membrane-bound arachidonic acid is freed and converted to unstable intermediate PGH₂ by COX, which has two forms: constitutive COX-1 and inducible COX-2. Short-lived PGH₂ is then quickly converted to five prostanoids, consisting of prostaglandin PGD₂, PGE₂, PGF_2α, prostacyclin PGI₂, and thromboxane TXA₂, by tissue-specific prostanoid synthases. Prostanoids exert their functions via activating a suite of GPCRs. Four receptors – EP1, EP2, EP3 and EP4 – are activated by PGE₂, and two by PGE₂ (DP1 and DP2), whereas each of the other three prostanoids activates a single receptor (FP, IP, TP). The inflammatory prostaglandin signaling is mainly mediated by PGE₂ and its receptors. Only the major pathways are shown. (B) Chemical structures of example small molecules that selectively block prostaglandin PGE₂ receptor subtype EP2. The potency (Schild K_B) and selectivity of each compound are indicated. (C) Chemical structures of small molecules that selectively block EP1 receptor. The potency (Ki) and selectivity of each compound are indicated. Abbreviations: COX, cyclooxygenase; GPCRs, G protein-coupled receptors; PG, prostaglandin; PGES, prostaglandin E synthase.