Composés et métabolites pharmaceutiques et vétérinaires

15-deoxy-Δ12,14-Prostaglandin D2 (15-deoxy-Δ12,14-PGD2) is a PGD2 metabolite functioning as an agonist for the PGD2 receptor 2 (DP2), with a binding affinity (Ki) of 50 nM for the mouse DP2 receptor expressed in HEK293 cell membranes. It activates eosinophils with an EC50 of 8 nM and enhances the recruitment of steroid receptor coactivator-1 (SRC-1) to peroxisome proliferator-activated receptor γ (PPARγ), initiating PPARγ-mediated transcription at 5 µM concentration. Furthermore, it exhibits cytotoxicity towards L1210 murine leukemia cells with an IC50 of 0.3 µg/ml and displays weaker inhibition of ADP-induced platelet aggregation than PGD2, with an IC50 of 320 ng/ml.

N-Acyl taurines, such as N-lignoceroyl taurine, alongside various arachidonoyl amino acid conjugates like N-arachidonoyl dopamine and N-arachidonoyl-L-serine, have been identified in bovine brain and through mass spectrometry lipidomic studies in the brain and spinal cord of both wild-type and FAAH knockout mice. Notably, N-lignoceroyl taurine levels were found to be 23-26 times higher in FAAH knockout mice than in wild types, suggesting its degradation by FAAH, despite in vitro evidence showing FAAH hydrolyzes N-lignoceroyl taurine significantly slower than oleoyl ethanolamide. Additionally, N-acyl taurines with polyunsaturated acyl chains are known to activate TRPV1 and TRPV4 channels within the transient receptor potential (TRP) family of calcium channels.

<p>Prostaglandin H2 (PGH2), initially isolated from the incubation of arachidonic acid with ovine seminal vesicle microsomes, acts as a potent vasoconstrictor. It serves as the precursor for all 2-series prostaglandins (PGs) and thromboxanes (TXs). Moreover, as a TP receptor agonist, PGH2 irreversibly aggregates human platelets at concentrations of 50-100 ng/ml.</p>

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are lipids recently discovered to be modulated by dietary influences such as fasting and high-fat feeding, and they play a role in enhancing insulin sensitivity. These compounds typically feature a carbon-16 or carbon-18 fatty acid (e.g., palmitoleic, palmitic, oleic, or stearic acid) esterified to a carbon-16 or carbon-18 hydroxy fatty acid. A specific example is 12-SAHSA, which consists of stearic acid linked to 12-hydroxy stearic acid. Notably, 12-SAHSA levels are found to be moderately increased in the serum of glucose tolerant AG4OX mice, a model characterized by adipose tissue-specific overexpression of the Glut4 glucose transporter.

<p>13,14-Dihydro-15(R)-Prostaglandin E1 (13,14-dihydro-15(R)-PGE1) is an analog of 13,14-dihydro-PGE1 characterized by its R-configured hydroxyl group at the C-15 position [1].</p>

12,15-Epoxy-13-methyl-12,14-eicosadienoic acid, a furan fatty acid first identified in northern pike (E. lucius), exhibits elevated levels in the liver of starving cod.

<p>N8-Acetylspermidine dihydrochloride is a polyamine that regulates ischemic cardiac apoptosis and resultant cardiac dysfunction.</p>

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are recently discovered lipids that play a role in the body's response to fasting and high-fat diets, with a link to insulin sensitivity. These compounds consist of a long-chain fatty acid (such as palmitoleic, palmitic, oleic, or stearic acid) bonded to a hydroxy fatty acid, both ranging in length from C-16 to C-18. Specifically, 12-OAHSA is a type of FAHFA where oleic acid is attached to the 12th carbon of hydroxy stearic acid. Within the FAHFA family, OAHSAs are particularly notable for their high concentration in the serum of AG4OX mice, a strain engineered to express the Glut4 glucose transporter predominantly in their adipose tissue, which demonstrates an enhanced glucose tolerance.

<p>1,2-Dioleoyl-3-linoleoyl-rac-glycerol (OOL) is a triglyceride featuring oleic acid at the sn-1 and sn-2 positions and linoleic acid at the sn-3 position. This compound is prevalent in several seed and vegetable oils, such as those from pumpkin seeds, olives, and sesame.</p>

<p>Metformin hydroxy analog 2, an oxidation product of the biguanide metformin (1), represents a chemically transformed variant of the original compound, showcasing a modified molecular structure through the process of oxidation.</p>

cis-9,10-Epoxystearic acid (cis-9,10-Epoxyoctadecanoic acid) is an endogenous component in human urine and blood and can be produced from oleic acid by enzymic

1,2,3-Tritricosanoyl glycerol, a triacylglycerol containing tricosanoic acid at the sn-1, sn-2, and sn-3 positions, serves as an internal standard for the quantification of fatty acids within the triglyceride component of human aortic endothelial cells (HAECs) cultured in media supplemented with stearic and/or oleic acid.

(R)-Palmitoyl-(2-methyl)ethanolamide (Me-PEA) acts as a competitive inhibitor against [3H]-AEA metabolism, exhibiting a K i value of 6.6 μM [1].

10-OAHSA is a newly discovered endogenous lipid categorized within the group of branched fatty acid esters of hydroxy fatty acids (FAHFAs). This specific FAHFA comprises oleic acid esterified to 10-hydroxy stearic acid. It stands out among its FAHFA counterparts for its potential bioactive properties, similar to other members of its family such as PAHSAs, which are notably prevalent in the adipose tissue of AG4OX mice exhibiting glucose tolerance due to overexpression of the Glut4 glucose transporter specifically in adipose tissue. Like other FAHFAs, 10-OAHSA may play significant roles in enhancing glucose tolerance, stimulating insulin secretion, and exerting anti-inflammatory effects, which suggests its importance in managing metabolic syndrome and inflammation.

<p>L-DABA hydrobromide (L-2,4-Diaminobutyric acid hydrobromide) , GABA transaminase inhibitor with antitumor and anticonvulsant activity.</p>

GNTI TFA is a selective kappa opioid receptor antagonist.

Zaragozic acid C is an effective inhibitor of squalene synthase.

YM-355179 is a novel, selective antagonist of CC chemokine receptor 3 with oral activity.

MCTR3, derived from DHA via maresin 1 in macrophages, hastens tissue healing and reduces inflammation and eicosanoids post-E. coli infection in mice.

Tauro-ω-muricholic acid sodium (TωMCA sodium) is an analogue of tauro-α-muricholic acid, a bile acid of hepatic origin.

Isoprostanes are produced by the non-enzymatic, free radical peroxidation of phospholipid-esterified arachidonic acid.

7(Z),11(Z)-Nonacosadiene, a female fly pheromone, spurs male courtship; it's a C29 diene made by a female-specific elongase.

(+)-Potassium Ds-threo-isocitrate monobasic is a bioactive compound known for its role in enhancing cellular metabolism and regulating energy production. This substance is also utilized in researching metabolic pathways and the regulation of enzyme activities. Widely applied in biochemical research, (+)-Potassium Ds-threo-isocitrate monobasic is studied for its potential functions in cellular processes and disease mechanisms.

Homomoschatoline is an antibacterial isolated from Artabotrys crassifolius.

AubipyOMe serves as an effective inhibitor of Tartrate-resistant Acid Phosphatase (TRAP/ACP5), a metalloenzyme identified in activated osteoclasts and macrophages. It exhibits inhibitory IC50 values of 1.3 μM against TRAP5a and 1.8 μM against TRAP5b. Additionally, it effectively suppresses TRAP activity in extracts from mouse macrophages and human lung tissues.

<p>Mesembrine is a serotonin reuptake inhibitor and is also a weak inhibitor of the enzyme phosphodiesterase 4 (PDE4).</p>

Rostratin A, a disulfide from Exserohilum rostratum, is cytotoxic to HCT-116 cells with an IC50 of 8.5 μg/mL.

IDX375 is a non-nucleoside inhibitor that selectively targets the HCV NS5B enzyme. It shows promising selectivity for genotypes 1a and 1b. The structure and binding sites of IDX375 have been confirmed through X-ray co-crystallization studies.

<p>7-Hydroxychlorpromazine, an active metabolite of Chlorpromazine, can reversibly counteract the suppression of regionally dense dopaminergic neurons induced by Amphetamine.</p>

<p>Pyrocatechol sulfate, a phenolic metabolite found in human plasma, is associated with the intake of specific foods such as berries and the state of the gut microbiome. It serves as a potential urinary biomarker for kidney function, dialysis clearance rates, whole grain consumption, and regular coffee intake. Additionally, in conjunction with other phenolic sulfates, pyrocatechol sulfate plays a role in regulating various biological functions, including those related to brain health and the rhythmic beating of cardiac cells.</p>

Squalestatin 3 is an inhibitor of squalene synthase.

D-2-Phosphoglyceric acid is a crucial metabolic intermediate known for its role in enhancing cellular energy metabolism and regulating biosynthesis. It plays a key role in both glycolysis and photosynthesis, which are essential for cellular energy supply. Additionally, D-2-Phosphoglyceric acid serves as a biomarker for monitoring metabolic states in various organisms.

<p>Fusarisetin A, a pentacyclic fungal metabolite, is an acinar morphogenesis inhibitor .</p>

RS 61756-007 is a selective thromboxane receptor (TP) agonist.

Rostratin B, a cytotoxic disulfide, demonstrates in vitro cytotoxicity against human colon carcinoma (HCT-116), exhibiting an IC50 value of 1.9 μg/mL.

OH-α-PVP (OH-α-Pyrrolidinovalerophenone) TFA is a metabolite of α-pyrrolidinovalerophenone, which is a synthetic cathinone stimulant.

Sphingomyelin (d18:1/12:0) is a polar lipid known for its role in modulating cell signal transduction. It plays a critical role in cell membranes, influencing their fluidity and stability. Additionally, sphingomyelin (d18:1/12:0) is involved in lipid metabolism and has potential in promoting neuronal cell growth. This compound is essential for the functioning and development of the nervous system.

DOCP (2-((2,3-Bis(oleoyloxy)propyl)dimethylammonio)ethyl hydrogen phosphate) is a lipid characterized by an opposite charge orientation compared to traditional phosphatidylcholine (PC) lipids, featuring quaternary ammonium near the bilayer interface and phosphate groups projecting into the aqueous environment. This unique structure of iPC lipids presents an excellent opportunity to investigate the biophysical characteristics and biological activities influenced by the reversal of surface charges on bilayers.

UM-3006 is a potent TLR7/8 agonist that enhances immune responses by activating the TLR signaling pathway. This compound holds significant research and application potential in the fields of vaccine adjuvants and immune diseases.

3-Oxochenodeoxycholic acid is an endogenous metabolite detectable in feces and may serve as a diagnostic marker for various diseases, including COVID-19.

Calcium 2-hydroxypropanoate (pentahydrate) acts as an activator of the hydroxyl-carboxylic acid receptor 1 (HCAR1) and serves as an epigenetic regulator that induces lysine residue lactylation. This compound, a glycolysis end product, bridges the gap between glycolysis and oxidative phosphorylation and functions as a tumor metabolite with immunoprotective effects of lactate in antitumor immunity.

NADH-IN-2 (compound 8) is a Type II NADH dehydrogenase inhibitor.

<p>Estradiol 3-glucuronide is an immunogen with antigenic properties. The antiserum induced in rabbits exhibits high affinity and specificity for Estradiol 3-glucuronide. This compound shows promise for use in research involving radioimmunoassay.</p>

S-MTC acetate (S-Methyl-L-thiocitrulline acetate) serves as a potent inhibitor of inducible nitric oxide synthases and is especially effective in inhibiting the constitutive (neuronal) type rather than the inducible (endothelial) type.

<p>Magnesium ionophore III (ETH 4030) is an ion carrier that regulates intracellular magnesium ion concentrations. It enhances cellular functions and metabolic activities by increasing the permeability of cell membranes to magnesium ions. Additionally, Magnesium ionophore III is utilized in research to explore the significance of magnesium ions in biological processes and their impact on cellular physiology.</p>

9(Z),12(E)-Octadecadienoic Acid (C18:2(9E,12Z); C18:2 n-6), an isomer of linoleic acid, is a type of ω-6 polyunsaturated fatty acid containing a trans double bond at the C9 position. It is identified as a minor component in milk fat and partially hydrogenated vegetable oils. The concentration of 9(Z),12(E)-Octadecadienoic Acid in rabbit meat increases following supplementation with heated sunflower seed oil, α-tocopherol acetate, and zinc.

<p>9(S)-HETE is an enantiomer of (±)9-HETE, not an enzymatic product, and doesn't promote cell adhesion like 12(S)-HETE. Identified by chiral HPLC.</p>

Cephapirinlactone is a metabolite of the antibiotic Cephapirin.

15:0 PG sodium serves as an activator for the Protein Kinase C family and is an anionic phospholipid located in the membranes of mitochondria and microsomes. It plays a crucial role in the composition of pulmonary surfactants, especially within the membrane of the pulmonary lamellar bodies.

Dioctanoylphosphatidic acid sodium serves as a modulator of phagocyte respiratory bursts, a precursor to diacylglycerol and lyso-phosphatidic acid, and influences the phosphorylation of the mammalian target of rapamycin (mTOR). Additionally, it enhances the viability of gallbladder cancer cells inhibited by histone deacetylase inhibitors (HDACI). This compound is derived from glycerophospholipids through the action of phospholipase D.