Doconexent API Manufacturers

General Description:

Doconexent, identified by CAS number 6217-54-5, is a notable compound with significant therapeutic applications. A mixture of fish oil and primrose oil, doconexent is used as a high-docosahexaenoic acid (DHA) supplement. DHA is a 22 carbon chain with 6 cis double bonds with anti-inflammatory effects. It can be biosythesized from alpha-linolenic acid or commercially manufactured from microalgae. It is an omega-3 fatty acid and primary structural component of the human brain, cerebral cortex, skin, and retina thus plays an important role in their development and function. The amino-phospholipid DHA is found at a high concentration across several brain subcellular fractions, including nerve terminals, microsomes, synaptic vesicles, and synaptosomal plasma membranes .

Indications:

This drug is primarily indicated for: Used as a high-docosahexaenoic acid (DHA) oral supplement. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Doconexent undergoes metabolic processing primarily in: DHA can be metabolized into DHA-derived specialized pro-resolving mediators (SPMs), DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids, among others. It is converted to 17-hydroperoxy-DHA derivatives via COX-2 and 15-LOX and 5-LOX activity. These derivatives are further converted into D-series resolvins and protectins with potent anti-inflammatory potential and potent neuroprotective effect . DHA may also be metabolized to 19,20-epoxydocosapentaenoic acids (EDPs) and isomers via CYP2C9 activity. Epoxy metabolites are reported to mediate anti-tumor activity by inhibiting angiogenesis, tumor growth, and metastasis. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Doconexent are crucial for its therapeutic efficacy: Like other omega-3 fatty acids, DHA is hydrolyzed from the intestines and delivered through the lymphatic circulation. Plasma DHA concentrations increase in a dose-dependent and saturable manner. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Doconexent is an important consideration for its dosing schedule: Approximately 20 hours . This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Doconexent is distributed throughout the body with a volume of distribution of: DHA is the most abundant n−3 fatty acid in membranes and is present in all organs. It is also the most variable among organs and is particularly abundant in neural tissue, such as brain and retina, where it is several hundred-fold more abundant than EPA . This metric indicates how extensively the drug permeates into body tissues.

Pharmacodynamics:

Doconexent exerts its therapeutic effects through: DHA in the central nervous system is found in the phospholipid bilayers where it modulates the physical environment and increase the free volume within the membrane bilayer. It influences the G-protein coupled receptor activity and affects transmembrane transport and cell interaction with the exterior world. It is also reported to promote apoptosis, neuronal differentiation and ion channel activity. Like other polyunsaturated fatty acids, DHA acts as a ligand at PPARs that plays an anti-inflammatory effect and regulate inflammatory gene expression and NFκB activation. DHA also gives rise to resolvins and related compounds (e.g, protectins) through pathways involving cyclooxygenase and lipoxygenase enzymes to resolve the inflammatory responses. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Doconexent functions by: DHA and its conversion to other lipid signalling moleccules compete with the arachidonic acid cascade from endogenous phospholipids and shift the inflammatory state to being more anti-inflammatory. DHA inhibits endotoxin-stimulated production of IL-6 and IL-8 in human endothelial cells. Derivatives of DHA are anti-inflammatory lipid mediators. Lipid mediators resolvin D1 and protectin D1 all inhibit transendothelial migration of neutrophils, so preventing neutrophilic infiltration at sites of inflammation, resolvin D1 inhibits IL-1β production, and protectin D1 inhibits TNF and IL-1β production . Monoxydroxy derivative of DHA converted by LOX inhibit thromboxane-induced platelet aggregation. DHA supplementation has also shown to reduce the levels of serum C-reactive protein (CRP) and other circulating markers of inflammation such as neutrophils in hypertriglyceridemic men . DHA acts as a ligand at peroxisome proliferator-activated receptor (PPAR) gamma and alpha that regulate lipid signalling molecule-mediated transduction pathways and modulate inflammation. As a natural ligand, DHA induces a protective effect in retinal tissues by activating retinoid x receptors and subsequent ERK/MAPK signaling pathway in photoreceptors to promote their survival and differentiation, stimulating the expression of antiapoptotic proteins such as Bcl-2 and preserving mitochondrial membrane potential . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Doconexent belongs to the class of organic compounds known as very long-chain fatty acids. These are fatty acids with an aliphatic tail that contains at least 22 carbon atoms, classified under the direct parent group Very long-chain fatty acids. This compound is a part of the Organic compounds, falling under the Lipids and lipid-like molecules superclass, and categorized within the Fatty Acyls class, specifically within the Fatty acids and conjugates subclass.

Categories:

Doconexent is categorized under the following therapeutic classes: Cytochrome P-450 CYP2C9 Inhibitors, Cytochrome P-450 CYP2C9 Inhibitors (strength unknown), Cytochrome P-450 CYP2C9 Substrates, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Substrates, Dietary Fats, Dietary Fats, Unsaturated, Fats, Fatty Acids, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Fish Oils, Lipids, Oils. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.