12-epi Leukotriene B4

Leukotriene B4 (LTB4) compounds are produced by both enzymatic and non-enzymatic processes. The products of enzymatic origin, via Leukotriene A4 (LTA4) hydrolase, are stereospecifically 12 (R) . Non-enzymatic hydrolysis products are 50:50 mixtures at C-12, but are almost exclusively trans at C-6. Thus, the non-enzymatic hydrolysis product of LTA4 is 6-trans-12-epi LTB4. 12-epi LTB4 is an isomer which would not be expected to occur in either non-enzymatic hydrolysis products, or in the enzymatic products of LTA4 hydrolase. Compared to LTB4, 12-epi LTB4 has significantly reduced activity for the LTB4 receptor on human neutrophils (IC50 of 7.5 mM), and on guinea pig lung membranes with a (Ki of 4.7 mM) . 12-epi LTB4 is an weak agonist at both the recombinant human BLT1 and BLT2 receptors, requiring approximately 10 mM for full activation of the receptor.