XEN445 XEN445;2-[(3S)-3-(2-Pyridinylmethoxy)-1-pyrrolidinyl]-5-(trifluoromethyl)benzoic acid;(S)-2-(3-(pyridin-2-ylmethoxy)pyrrolidin-1-yl)-5-(trifluoromethyl)benzoic acid;2-[(3S)-3-(2-Pyridinylmethoxy)-1-py 1515856-92-4
XEN445 is a potent and selective EL inhibitor(IC50=0.237 uM), that showed good ADME and PK properties, and demonstrated in vivo efficacy in raising plasma HDLc concentrations in mice.
IC50 value: 0.237 uM [1]
Target: Endothelial lipase inhibitor
XEN445 can be readily prepared in good yield from commercial
available chemicals, which was selected for further evaluation of
this series of EL inhibitors. After a 30 min preincubation of EL-expressing HEK cells with XEN445, the IC50 value for XEN445 of 0.25 lM was obtained. This value was very similar to that determined in the cell-free assay. Wild-type mice were orally dosed with XEN445 at 30 mg/kg b.i.d. for 3 days and blood was taken on the morning of day 4, 16 h post nal dose. At termination, the average plasma levels of XEN445 was 9.9 lM and the drug caused an 18% and 16% increase in total plasma cholesterol and HDLc, respectively.
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