SC 26196

The enzyme ?6 desaturase mediates the conversion of linoleic acid to ?-linolenic acid (GLA), which can then be elongated to dihomo-?-linolenic acid (DGLA). DGLA can then be used as a substrate for ?5 desaturase to produce arachidonic acid (AA), the fatty acid that is used to generate eicosanoids. SC 26196 is an inhibitor of ?6 desaturase (IC50 = 0.2 µM in a rat liver microsomal assay) that completely blocks the conversion of linoleic acid to arachidonic acid (AA).{29588} It is selective for ?6 desaturase, as IC50 values for ?5 and ?9 desaturases exceed 200 µM and it has no effect on the conversion of dihomo-?-linolenic acid to AA.{29588,29586} SC 26196 is orally active in vivo, decreasing edema in the carrageenan paw edema model in mice.{29588} It also blocks aging-related increases in AA in myocardial cardiolipin in mice, attenuating contractile dysfunction without impacting mitochondrial oxidative stress.{29587}