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Therapeutics

Unlocking the Full Potential of Omega 3 Biology

The health benefits of omega-3 fatty acids, commonly known as fish oil, are well known.

Targeting the molecular mechanism behind their protective action promises a high potential to treat diseases with high unmet need.

Recent discoveries show a crucial role of certain bioactive lipids formed from omega-3 fatty acids to serve as the mediator of the beneficial health effect – the so called “epoxyeicosanoids”.

Omega-3 epoxyeicosanoids, such as 17,18-EEQ and 19,20-EDP, are transformed by CYP P450 enzymes from EPA and DHA as the major omega-3 fatty acids.


17,18-EEQ and 19,20-EDP can mediate anti-inflammatory and cell-protective activity already at concentrations 1.000 times below EPA and DHA levels. However, they are metabolically very unstable, therefore rapidly degraded by the body’s enzymes and thus their natural levels remain very low. Furthermore, their formation and activity vary from individual to individual due to a person’s unique genetic make-up. Several diseases further promote deficiency of these protective molecules. These effects might also explain inconsistent results of clinical studies with omega-3 fatty acid treatments in different diseases.


OMEICOS’ approach overcomes these limitations. 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 the biological activity of their natural counterparts and are independent of dietary supplements and genetic factors of the individual.


OMEICOS’ molecules are specifically activating the AMPK/Sirt1/PGC1-a network and thereby mediating cell protective, anti-inflammatory and anti-fibrotic properties. A key element of the mechanism of action is the improvement of mitochondrial function in cells, a central factor for cell homeostasis in disease conditions.


OMEICOS’ compounds are orally available, safe and convenient to use, and show significantly improved biological activity and pharmacokinetic properties compared to their natural counterpart.

OMT-28’s Mode of Action targets a key regulator network for cell metabolism and mitochondrial function

OMEICOS’ in-depth knowledge about OMT-28’s Mode of Action leads to the therapeutic rationale of reducing inflammation and improving primary and secondary forms of mitochondrial dysfunctions in diseases with high unmet medical need.

 

Our Scientific Library

Chemistry
Scientific Evidence
Therapeutic Potential Clinical Application
Chemistry

Development of robust 17,18‑EEQ analogs as potential clinical antiarrhythmic agents

Adebesin et al. J Med Chem 2019

VISIT

Development of metabolically robust 17,18-EEQ analogs

Falck et al. J Med Chem 2011

VISIT

Scientific Evidence

Cardioprotective effects of CYP-derived epoxymetabolites of docosahexaenoic acid involve limiting NLRP3 inflammasome activation

Darwesh et al. Can J Physiol Pahrmacol 2019

VISIT

Novel Roles of Epoxyeicosanoids in Regulating Cardiac Mitochondria

El-Sikhry et al. PLoS One 2016

VISIT

17,18-EEQ becomes the major upregulated EPA-metabolite when omega-3 fatty acid supplementation is given to man

Fischer et al. J Lipid Res 2014
VISIT

In transgenic mice overexpression of human epoxygenase CYP2J2 confers protection against ventricular tachycardia and atrial fibrillation

Westphal et al. PLoS One 2013
VISIT

CYP-eicosanoids - a new link between omega-3 fatty acids and cardiac disease?

Westphal et al. Prostaglandins Other Lipid Mediat. 2011
VISIT

Role of cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids

Konkel and Schunck, Biochim Biophys Acta. 2011
VISIT

CYP enzymes efficiently convert EPA and DHA to novel bioactive lipid mediators that probably contribute to the cardiovascular beneficial effects of dietary omega-3 fatty acids. CYP2J2, the major CYP epoxygenase in the human heart prefers EPA as substrate and converts it to 17,18-EEQ

C Arnold et al. JBC 2010


VISIT

Relevance of soluble Epoxide Hydrolase (enzyme which is quickly de-activating 17,18-EEQ) in heart failure development – supporting evidence for relevance of CYP pathway as a therapeutic target in heart diseases

Monti et al. Nature Med 2008


VISIT

Therapeutic Potential Clinical Application

Amerlioration of endotoxemia by a synthetic analog of omega-3 epoxyeicosanoids

Shikuma et al. Front Immunol 2022

VISIT

Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids

Keshavarz-Bahaghighat et al. Cells 2020

VISIT

Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study

Berlin et al. Int J Cardiol Heart Vasc 2020

VISIT

Review: Therapeutic potential of omega-3 fatty acid-derived epoxyeicosanoids in cardiovascular and inflammatory diseases

Schunck et al. Pharmacol Ther 2018

VISIT

17,18-EEQ and stable synthetic analog C21 reduce chorideal neovascularization via a immunomodulatory mechanism of action

Hasegawa et al. PNAS 2017

VISIT

17,18-EEQ as active EPA metabolite, mediating reduction of chorideal neovascularization

Yanai et al. PNAS 2013

VISIT