Unlocking the Full Potential of Omega 3 Biology
The health benefits of an omega-3 fatty acid rich diet were first recognized when populations with traditionally high intake of fish and seafood were found to be less susceptible to cardiovascular-related mortality caused particularly by arrhythmia and sudden cardiac death. It turns out this and a variety of other beneficial health effects are actually mediated by omega-3 fatty acid-derived metabolites, called “epoxyeicosanoids”.
Epoxyeicosanoids as a novel class of omega-3 fatty acid-derived bioactive molecules are generated via the cytochrome P450 (CYP) epoxygenase pathway. Enzymes in the CYP pathway help to transform the major dietary fish oil omega-3 fatty acids, EPA and DHA, to omega-3 epoxyeicosanoids such as 17,18-EEQ and 19,20-EDP. Preclinical studies performed by OMEICOS and its partners showed that these molecules display cardioprotective, neuroprotective, anti-inflammatory and immune-modulating properties making them a potentially attractive novel class of bioactive molecules for the prevention and treatment of several diseases.
However, these molecules have proven to be highly unstable and are rapidly converted into metabolites with either no or less favourable biological activities. Furthermore, the formation and activity of these beneficial molecules vary from individual to individual due to a person’s unique genetic make-up and several diseases negatively impact this process, as well. Taken together, the bioavailability of epoxyeicosanoids in the human body is largely unpredictable.
Our approach aims to overcome these limitations in addition to making the drugs orally available. Based on in-depth structure-activity-relationship studies, we have generated a library of first-in-class, metabolically stable, synthetic analogs of epoxyeicosanoids that mimic their biological activity and are independent of dietary supplements and genetic factors that can modulate cellular metabolite levels. Our small molecule compounds are orally available and show significantly improved biological activity and pharmacokinetic properties compared to their natural counterpart.