If the primary alcohol is bonded to the phosphoserine part and the secondary alcohol is linked to the acyl group, we refer to the compound as 1p-2a type. Thus, the glycerol moiety was fixed by connecting the hydroxyl group of 2-glycerol alcohol to carbon 1 or 3 to provide four different core scaffolds of cyclic LysoPS analogues, including cis and trans isomers (Figure and Figure ). The fatty acid moiety is oleic acid (18:1), as in endogenous LysoPS (18:1) (1). The agonistic activities of the cyclic LysoPS derivatives were evaluated by means of TGF shedding assay. The results showed that both cis and trans core scaffolds having the acyl chain at the primary alcohol position of the tetrahydropyran ring were potent and selective for GPR34 (Table ). For the present computational analysis, we selected trans-1a-2p (EC50 = 100 nM, GPR34) and cis-1a-2p (EC50 = 210 nM, GPR34) as active ligands, and trans-1p-2a and cis-1p-2a as non-active ligands, together with endogenous LysoPS(18:1).