Fig. 4
From: Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator
Chemical structures of acidic steroid type- and phenylacetic acid (PAA) type-GSMs with their EC50 for decreasing Aβ42. 5β-Cholanic acid (1) has a four-ring structure with a 4-carbon side chain on carbon 17 and its EC50 for decreasing Aβ42 is ~5.7 μM. 25(R)-cholesteonic acid (2a) has the same four-ring structure with an additional hydroxyl group on carbon 3 and a 6-carbon side chain on carbon 17. For this molecule, the EC50 is at ~250 nM. EVP-0015962 (3), (R)-2-(5-chloro-6-(2,2,2-trifluoroethoxy)-4’-(trifluoromethyl)biphenyl-3-yl)-3-cyclobutylpropanoic acid, shows GSM activity at EC50 of 67 nM from the previous literature. GSM-1 (4) has the two phenyl rings with the carboxylic acid functional group. The EC50 for GSM-1 is at 92 nM