endocannabinoid

Anandamide ((5Z,8Z,11Z,14Z)-N-(2-Hydroxyethyl)icosa-5,8,11,14-tetraenamide) 是一种免疫调节剂，通过大麻素受体 CB1 和 CB2 起作用，还通过中枢神经系统中的其他靶点起作用，如 GPR18 GPR55。

MAGL-IN-4 (His121 ARG57) 是选择性的、口服有效的、可透过血脑屏障的、可逆的单酰基甘油脂肪酶抑制剂，IC50=6.2 nM。它主要通过大脑中选择性抑制 MAGL 增加 2-花生四烯酰甘油水平来增强内源性大麻素信号。

AM404 是一种内源性大麻素再摄取抑制剂，是 TRPV（1） 激活剂，是扑热息痛代谢物，具有神经保护作用和抗癌活性，可阻断 anandamide 转运。AM404 抑制 NFAT 和 NF-kappaB 信号通路，并损害神经母细胞瘤细胞的迁移和侵袭性，通过抑制 COX 活性来阻止活化的小胶质细胞中前列腺素的合成。

BIA 10-2474 是一种长效可逆的脂肪酸酰胺水解酶抑制剂，与人类内源性大麻素系统相互作用，可增加中枢神经系统和外周组织，对大鼠大脑不同区域的 IC50值为50至70mg kg。它用于治疗焦虑症、帕金森氏病和多发性硬化症、高血压或肥胖症的慢性疼痛。

endocannabinoid transport inhibitor

(±)10(11)-EDP ethanolamide is an ω-3 endocannabinoid epoxide and cannabinoid (CB) receptor agonist (EC50s = 0.43 and 22.5 nM for CB1 and CB2 receptors, respectively). It is produced though direct epoxygenation of docosahexaenoyl ethanolamide by cytochrome P450 (CYP) epoxygenases. 10,11-EDP epoxide (12.5 and 25 μM) reduces the viability of 143B metastatic osteosarcoma cells. It induces apoptosis and inhibits cell migration in a wound-healing assay in 143B, MG63, and HOS osteosarcoma cells. (±)10(11)-EDP ethanolamide also reduces tube formation by human umbilical vein endothelial cells (HUVECs) in a Matrigel assay.

(±)19(20)-EDP ethanolamide is an ω-3 endocannabinoid epoxide and cannabinoid (CB) receptor agonist (EC50s = 108 and 280 nM for CB1 and CB2, respectively). It is produced through direct epoxygenation of docosahexaenoyl ethanolamide by cytochrome P450 (CYP) epoxygenases. (±)19(20)-EDP ethanolamide (25 μM) reduces the viability of 143B metastatic osteosarcoma cells. It decreases the production of IL-6 and increases the production of IL-10 when used at concentrations ranging from 2.5 to 10 μM in BV-2 microglia stimulated by LPS and decreases LPS-induced cytotoxicity when used at concentrations ranging from 5 to 10 μM. It also decreases nitrite production when used at a concentration of 7.5 μM, an effect that can be partially reversed by the CB2 receptor antagonist AM630 and the PPARγ antagonist GW 9662 . (±)19(20)-EDP ethanolamide induces vasodilation of isolated preconstricted bovine coronary arteries (ED50 = 1.9 μM) and reduces tube formation by human microvascular endothelial cells (HMVECs) in a Matrigel assay.

In humans, two forms of diacylglycerol lipase, DAGLα and DAGLβ, generate the endocannabinoid 2-arachidonoyl glycerol by attacking DAG at the sn-1 position. O-7460 is a selective inhibitor of 2-AG biosynthesis via DAGLα (IC50 = 690 nM). It demonstrates much weaker inhibition towards human monoacylglycerol lipase and rat brain fatty acid amide hydrolase (IC50s > 10 μM) and does not bind to CB1 or CB2 cannabinoid receptors (Kis > 10 μM). At 0-12 mg kg, i.p. in mice, O-7460 was reported to dose-dependently inhibit high-fat diet intake and reduce body weight.

Anandamide (arachidonoyl ethanolamide; AEA) is an endogenous lipid with cannabinergic activity; along with 2-arachidonoyl glycerol, it forms part of the endocannabinoid system. AEA undergoes reuptake into neurons by a facilitated process. Controversy exists as to whether there is a specific AEA transporter, or instead the uptake process is simply driven by hydrolysis of AEA by intracellular fatty acyl amide hydrolase (FAAH). CAY10412 is an analog of AEA that has no intrinsic binding affinity for either CB1 or CB2 receptors. It is a potent inhibitor of AEA reuptake in U937 lymphoma cells, with an IC50 of 3 μM. CAY10412 could be a useful tool for distinguishing the competing transporter theories. The pharmacology of CAY10412 is largely unexplored; it may enhance endocannabinoid signalling by augmenting endocannabinoid concentrations.

Virodhamine (O-arachidonoyl ethanolamine) 是一种内源性大麻素，是CB1受体的拮抗剂和CB2受体的激动剂。Virodhamine 可用于阿尔茨海默病等神经系统疾病的研究。

AMG-315 is a Potent Endocannabinoid Ligand with Stability to Metabolizing Enzymes. AMG-315 is a chiral arachidonoyl ethanolamide (AEA) analogue or (13S,1′R)-dimethylanandamide. AMG-315 is a high affinity ligand for the CB1 receptor (Ki of 7.8 ± 1.4 nM) that behaves as a potent CB1 agonist in vitro (EC50 = 0.6 ± 0.2 nM). AMG-315 is the first potent AEA analogue with significant stability for all endocannabinoid hydrolyzing enzymes as well as the oxidative enzymes COX-2. AMG-315 will serve as a very useful endocannabinoid probe.

WOBE437 is a selective endocannabinoid reuptake inhibitor which reduces disease progression in a mouse model of multiple sclerosis

Orlistat-d3 is intended for use as an internal standard for the quantification of orlistat by GC- or LC-MS. Orlistat is a digestive lipase inhibitor. It inhibits diacylglycerol lipase α (DAGLα), DAGLβ, α β-hydrolase domain-containing protein 12 (ABHD12), ABHD16A, and platelet-activating factor acetylhydrolase (PAF-AH; IC50s = 0.06, 0.1, 0.08, 0.03, and 0.05 µM, respectively), as well as pancreatic lipase and hormone-sensitive lipase (IC50s = 0.65 and 2.1 µg ml, respectively) but does not inhibit fatty acid amide hydrolase (FAAH) or KIAA1363 (IC50s = >100 µM for both). Orlistat decreases ionomycin-induced production of the endocannabinoid 2-arachidonoyl glycerol (2-AG) in N18TG2 murine neuroblastoma cells when used at a concentration of 1 µM. It also inhibits fatty acid synthase (FASN; Kiapp = ~0.1 µM for the human enzyme) and the proliferation of PC3 prostate cancer cells in a concentration-dependent manner. Orlistat (10 mg kg) decreases serum cholesterol levels and total bod......

JZP-MA-11是一种用于正电子发射断层扫描(PET)的配体，专一性靶向内源性大麻素α β-水解酶结构域6(ABHD6)酶，并具有126 nM的IC50值，表明其对ABHD6有选择性抑制作用。JZP-MA-11能有效穿过血脑屏障(BBB)。[18F]JZP-MA-11展现出在靶向小鼠及非人灵长类(NHP)大脑ABHD6方面的临床前评估潜力。

Linoleoyl ethanolamide 是脂肪酸乙醇酰胺。它可弱结合 CB1 和 CB2 受体，并分别抑制[3H]CP-55,940的结合，Ki 分别为 10 和 25μM。它在引起小鼠过氧化氢酶方面的效力是 anandamide 的4倍，且对睡眠时间无延长效果。

Tricosanoyl ethanolamide, a fatty N-acyl ethanolamine within the endocannabinoid family, has an ethanolamine metabolite whose significance remains to be established.

γ-Linolenoyl monoethanolamide，一种脂肪N-酰乙醇胺，属于内源性大麻素。

Lignoceroyl ethanolamide, a fatty N-acyl ethanolamine within the endocannabinoid family, is derived from lignoceric acid, which is found in relatively high concentrations in rat cerebrospinal fluid. However, the specific function and significance of this metabolite remain unclear.

Arachidoyl ethanolamide, a saturated fatty acyl ethanolamide lacking classical (CB1 CB2) activity, plays a role in a complex system comprising central cannabinoid (CB1), peripheral cannabinoid (CB2), and non-CB receptor-mediated pharmacology. This system has paved the way for extensive research in diverse fields such as memory, weight loss and appetite, neurodegeneration, tumor surveillance, analgesia, and inflammation. Unlike other compounds, Arachidoyl ethanolamide does not bind to the murine CB1 receptor nor does it compete with anandamide for the fatty acid amide hydrolase, the endocannabinoid hydrolytic enzyme. The non-CB receptor-mediated actions of saturated ethanolamides like Arachidoyl ethanolamide are currently under investigation.

N-Palmitoyl taurine, an amino-acyl endocannabinoid prominent in rat brain lipidomics profiling, accompanies multiple arachidonoyl amino acids isolated from bovine brain, including N-arachidonoylethanolamine (NADA) and N-arachidonoyl serine (ARA-S). Mass spectral lipidomic analysis of rat brain additionally revealed a series of fatty acyl amides with taurine. The function of N-Palmitoyl taurine is under investigation.

N-Arachidonoyl dopamine (NADA) and N-Arachidonoyl serine (ARA-S), among various arachidonoyl amino acids, have been extracted from bovine brain, while a novel series of fatty acyl amides of taurine were unearthed in rat brain through mass spectral lipidomic analysis, indicating the discovery of a new class of compounds also located in the kidney. These compounds are known to activate members of the transient receptor potential (TRP) family of calcium channels. Notably, N-Stearoyl taurine emerges as a significant amino-acyl endocannabinoid identified in rat brain lipidomics profiling.

N-Oleoyl taurine, an amino-acyl endocannabinoid isolated from rat brain, along with several arachidonoyl amino acids such as N-arachidonoyl dopamine and N-arachidonoyl serine, have been derived from bovine brain. Mass spectral lipidomics analysis of rat brain revealed a series of fatty acyl amides of taurine, marking the discovery of a new class of compounds. These compounds, found in the kidney, are known to activate members of the transient receptor potential (TRP) family of calcium channels, with N-Oleoyl taurine specifically potentially activating TRPV1 and TRPV4 channels.

N-Arachidonoyl-L-serine (ARA-S), a recently isolated endocannabinoid with a distinct activity profile that diverges from typical endocannabinoids, does not interact with central cannabinoid (CB1), peripheral cannabinoid (CB2) receptors, or vanilloid receptor 1 (VR1). Unlike other compounds, ARA-S (5 mg kg) counteracts the lowering of blood pressure induced by a 10 mg kg intravenous bolus of abnormal cannabidiol (Abn-CBD) in anesthetized rat models. Additionally, akin to Abn-CBD, ARA-S induces relaxation in isolated rat mesenteric arteries and abdominal aorta and promotes phosphorylation of Akt and mitogen-activated protein kinase (MAPK) in human umbilical vein endothelial cells (HUVEC). The mechanisms through which ARA-S and Abn-CBD exert their effects on vascular systems show variations and merit deeper investigation.

N-Linolenoylethanolamine (18:3 NAE) 为一种内源性大麻素，同时也是香草素受体(TRPV1)的激动剂。