Métabolisme

1,2-Distearoyl-3-oleoyl-rac-glycerol, a triacylglycerol, comprises stearic acid at the sn-1 and sn-2 positions and oleic acid at the sn-3 position. This compound is present in cocoa butter and vegetable oils.

Fatty acid amide hydrolase (FAAH), an enzyme responsible for the hydrolysis and inactivation of fatty acid amides like anandamide and oleamide, has been identified as a target by the potent FAAH inhibitor PHOP. PHOP demonstrates remarkable inhibitory activity with K_i values as low as 0.094 nM for human FAAH and 0.2 nM for rat FAAH. Additionally, through a proteomics assay focusing on the serine hydrolase enzyme family, to which FAAH belongs, PHOP's selectivity was evaluated, presenting IC_50 values of 1.1 nM against FAAH, 1.4 nM against triacylglycerol hydrolase (TGH), and greater than 100 µM against an uncharacterized hydrolase (KIAA1363). This specificity profile of PHOP underscores its potential for yielding precise outcomes in studies involving complex biological systems.

MMV009085 is a potent inhibitor of the Plasmodium falciparum hexose transporter (Pf HT1), with potential as an anti-malarial agent.

LB-60-OF61 is a NAMPT inhibitor, a NAMPT inhibitor that displays antiproliferative activity against MYC oncogene-dependent cancer cell lines.

Siguazodan (SKF 94836) is an effective, selective, orally active phosphodiesterase III ((PDE-III)) inhibitor with an IC50 of 117 nM.

15(S)-HEDE is produced from 11Z,14Z-eicosadienoic acid by 15-LO. 15(S)-HEDE is an inhibitor of RBL-1 cell 5-LO with an IC50 value of 26 μM.

F1874-108 functions as an inhibitor of both brassinosteroid biosynthesis and signal transduction [1].

JGB-1-155, serving as a positive allosteric modulator (N-PAMs), effectively enhances the activity of nicotinamide phosphoribosyltransferase (NAMPT) with an EC 50 of 3.29 μM. It mitigates oxidative stress by elevating NAD+ levels in THP-1 human monocytes and reduces TNFα-induced reactive oxygen species (ROS) in HT-22 cells [1].

17(R)-Resolvin D1 (17(R)-RvD1) is an aspirin-triggered epimer of RvD1 that equivalently inhibits human polymorphonuclear leukocyte migration across the endothelium (EC50= ~30 nM), a precursor to acute inflammation. Unlike RvD1, it resists rapid degradation by eicosanoid oxidoreductases. In a mouse peritonitis model, 17(R)-RvD1 dose-dependently reduces leukocyte infiltration, achieving up to a 35% decrease with a 100 ng dose. Additionally, its methyl ester derivative, designed to enhance its pharmacokinetic and distribution properties as a more lipophilic prodrug, can be converted back into the active acid form by intracellular esterases.

7,7-Dimethyl-(5Z,8Z)-eicosadienoic acid (DEDA, 5 μM) significantly impacts the response to βA(25-35) stimulation. It reduces the formation of ROS.

FABP4/5-IN-4 (compound E1) effectively inhibits FABP 4 and FABP 5, displaying IC50 values of 3.78 μM and 5.72 μM, respectively. It is significant in the management of metabolic disorders such as diabetes mellitus [1].

Safinamide acid, a potential impurity in commercial safinamide preparations and a degradation product of safinamide under thermal and oxidative stress, is encountered in the pharmaceutical formulation process.

BML-288 is a phosphodiesterase Type II (PDE2) inhibitor that demonstrates no inhibition of 5-lipoxygenase (5-LO) or cyclooxygenase (COX-1).

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.

ICMT-IN-30 (compound 67) is an ICMT inhibitor with an IC50 value of 0.27 μM [1].

1,2-Diheptadecanoyl-sn-glycero-3-phosphorylcholine (DHPC) is a derivative of phosphatidylcholine (PC) that exhibits biological activity, functioning as a

RORγt agonist 2 is a potent agonist of RORγt.

SREBP/SCAP-IN-2 (compound 13) acts as a selective inhibitor of SREBP/SCAP [1].

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) have emerged as significant regulators of metabolic processes, influenced by dietary changes such as fasting and high-fat diets, and are linked to improved insulin sensitivity in mice. These compounds typically feature a fatty acid chain, either C-16 or C-18 in length (for example, palmitoleic, palmitic, oleic, or stearic acid), esterified to a hydroxy fatty acid of similar length. A specific FAHFA, 12-POHSA, involves the esterification of palmitoleic acid to the 12th carbon of stearic acid. Notably, 12-POHSA levels are markedly higher in the serum of AG4OX mice, which exhibit enhanced glucose tolerance due to overexpression of the Glut4 glucose transporter in adipose tissue. Given the capacity of FAHFAs to enhance glucose tolerance, stimulate insulin secretion, and exert anti-inflammatory actions, 12-POHSA holds potential as a bioactive lipid implicated in managing metabolic syndrome and inflammation.

A 79175 is a 5-lipoxygenase inhibitor that increases bone formation.