IC50 structure-activity relationship

The structure activity relationship (SAR) and animal model studies of biaryl benzamide MTP inhibitors 3 and 4 have also been reported. Compound 3 has an IC50 of 0.5 nM against human MTP in an in vitro assay and showed normalization of plasma lipoprotein levels in Watanabe-heritable hyperlipidemic rabbits,... 

A systematic study has confirmed the low activity of EHs toward cycloalkene oxides (1,2-epoxycycloalkanes, 10.123) [184], In the presence of mouse liver microsomal EH, activity was very low for cyclopentene oxide and cyclohexene oxide (10.123, n = 1 and 2, respectively), highest for cyclo-heptene oxide (10.123, n = 3), and decreased sharply for cyclooctene oxide (10.123, n = 4) and higher homologues. Mouse liver cytosolic EH showed a different structure-activity relationship in that the highest activity involved cyclodecene oxide (10.123, n = 6). With the exception of cyclohexene oxide, which exhibited an IC50 value toward microsomal EH in the p.M range, cycloalkene oxides were also very weak inhibitors of both microsomal and cytosolic EH. 

The investigation carried out on some Chinese animals used for CNS symptoms similar to those seen in AD resulted in the isolation of long chain fatty acids from the centipede Scolopendra subspinipes mutilans which had weak AChEl activity.A series of fatty acids was tested to discern any structure-activity relationships and it was found that only free acids, not esters, had AChEl activity. The presence of unsaturated bonds and a chain length of not less than 16 C were was necessary for activity. The most active compound tested was linolenic acid (71) with IC50 of 59.9 xM against AChE. 

In a structure-activity relationship study, it was found that the acetylation of gliovectin (54) made it less active with IC50 of 1 000 xM. 

Flavonoids, especially flavones and flavonols, also directly bind to several CYP isoforms (lAl, 1A2, IBl, 3A4) involved in xenobiotics metabolism and inhibit enzyme activity. Structure-activity relationships show rather high isoform selectivities depending on the flavonoid substitution pattern and contrasted inhibition mechanisms. For instance, inhibition by flavonoids of 7-methoxyresorufin O-demethylation in microsomes enriched in CYP lAl and 1A2 reveals that galangin (3,5,7-trihydroxyflavone) is a mixed inhibitor of CYP 1A2 (.ST = 8 nM) and a five times less potent inhibitor of CYP 1A1. By contrast, 7-hydroxy flavone is a competitive inhibitor of CYP lAl (Aii = 15 nM) and a six times less potent inhibitor of CYP 1A2. In addition, fairly selective inhibition of CYP IBl (specifically detected in cancer cells) by some flavonoids has been reported. For example, 5,7-dihydroxy-4 -methoxyflavone inhibits IBl, 1 Al, and 1A2 with IC50 values of 7, 80, and 80 nM, respectively. ... 

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