Metabolism

JP104 is an aryl carbamate that irreversibly inhibits fatty acid amide hydrolase (FAAH) with a pIC50 value of approximately 8 [1].

Leukotriene C4 (14,15-LTC4) is an inflammatory mediator synthesized from arachidonic acid through the actions of 15- and 12-lipoxygenases (LOs), involving intermediates such as 15-HpETE and 14,15-LTA4. Unlike the majority of leukotrienes formed via the 5-LO pathway, 14,15-LTC4 is an eoxin predominantly produced by eosinophils, although mast cells and nasal polyps can also synthesize it. While its physiological roles are not well understood, 14,15-LTC4 exhibits limited contractile activity on guinea pig ileum and pulmonary parenchyma. However, it can increase vascular permeability in human endothelial cell monolayers in vitro with potency comparable to 5-LO-derived leukotrienes, contributing to plasma leakage characteristic of inflammation.

5-OP-RU is a MAIT-activating ligand, a major antigen of MAIT cells, a mucosal adjuvant, and can be used to study Mycobacterium tuberculosis infection.

VULM 1457 is a potent ACAT inhibitor.

Dieicosanoin is a diacylglycerol that incorporates arachidic acid, a saturated long-chain fatty acid featuring a 20-carbon backbone. This acid is derivable from sources such as peanut butter and anaerobic fungi [1] [2].

Yonkenafil HCl, a PDE5 inhibitor, is used potentially for the treatment of erectile dysfunction.

8(Z),14(Z)-Eicosadienoic Acid, an ω-8 C20:2 fatty acid, constitutes 0.19% of total fatty acids in human milk. In vivo, it is converted by desaturases into eicosatrienoic acids, known for their potent vasodilator properties. However, the physiological effects of 8(Z),14(Z)-Eicosadienoic Acid remain unexplored.

Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are recent discoveries in endogenous lipids that are influenced by dietary changes such as fasting and high-fat diets, showing a link with enhanced insulin sensitivity in mice. These compounds typically feature a C-16 or C-18 fatty acid (e.g., palmitoleic, palmitic, oleic, or stearic acid) bound to a hydroxy group on another C-16 or C-18 fatty chain. A specific FAHFA, 9-POHSA, consists of palmitoleic acid connected at the hydroxy stearic acid's 9th position. This molecule, in particular, exhibits notably increased levels in the serum of glucose-tolerant AG4OX mice, which express the Glut4 glucose transporter predominantly in their adipose tissue. Given the broader family of FAHFAs' roles in enhancing glucose tolerance, promoting insulin secretion, and exerting anti-inflammatory effects, 9-POHSA emerges as a potential bioactive lipid involved in managing metabolic syndrome and inflammation.

ICMT-IN-28 (compound 65) serves as an inhibitor of ICMT, exhibiting significant potency with an IC50 value of 0.008 μM [1].

FXIa-IN-1 is a potent β-lactam covalent heparin-derived factor XIa (fXIa) inhibitor.

UCPH-102: Selective EAAT1 inhibitor, IC50 0.43 μM, treats Alzheimer's, ALS, chronic pain, OCD; crosses blood-brain barrier, targets T-ALL cells.

Phenylpyropene C inhibits JAK/STAT and IFN-γ expression (IC50: 5.4-10.8 μM), also blocks acyl CoA (IC50: 16.0 μM).

Dinophysistoxin 1 (DTX 1, 35-methylokadaic acid), a causative agent of diarrhetic shellfish poisoning, exhibits tumor-promoting activity and also acts as a skin

Monohydroxy melphalan, a degradation product and DNA alkylating agent derived from melphalan, results from melphalan hydrolysis in aqueous solutions such as cell culture medium and human plasma. It enhances DNA adducts in ML-1 myeloblastic leukemia cells based on concentration and induces cytotoxicity with an IC50 value of 28.1 μg/ml.

R-1663 inhibits factor Xa, prolongs clotting, reduces thrombin without affecting bleed time; more effective on peak than ETP.

Magmas-IN-1 (compound 9), a small molecule Magmas inhibitor (SMMI), targets the mitochondria-associated granulocyte-macrophage colony-stimulating factor (GM-CSF

Dendrogenin A (DDA) is a compound acting as a selective liver X receptor (LXR) modulator, cholesterol epoxide hydrolase inhibitor (Ki = 120 nM), and a metabolic

EMD638683 is a highly selective SGK1 inhibitor with IC50 of 3 μM. EMD638683 R-Form is the R-form of EMD638683.

ICMT-IN-46 (compound 25) is a potent inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), exhibiting an IC50 value of 0.556 μM [1].

Tetramyristoylcardiolipin (TMCL), an anionic lipid, plays a crucial role in studying cell membrane function and drug delivery mechanisms [1].

NTE-122 is a competitive Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor.

CKD-519: A CETP inhibitor with an IC50 of 2.3 nM, blocking cholesteryl ester transfer in serum.

FM26, an isoxazole-based RORγt inverse agonist, cuts EL4 IL-17a mRNA; potent with 264 nM IC50.

YG1702, a potent inhibitor specific to ALDH18A1, suppresses the proliferation of MYCN-amplified neuroblastoma (NB) and reduces MYCN expression.

LFHP-1c, a neuroprotective PGAM5 inhibitor, demonstrates efficacy in preserving blood-brain barrier integrity following ischemic stroke.

L-690488 has more effective cell penetration than L-690330. L-690488 is a prodrug of L-690330 and is a selective inositol monophosphatase (IMPase) inhibitor.

DAO-IN-1 (compound 10) is a potent DAO (D -amino acid oxidase) inhibitor that ameliorates schizophrenia by increasing D -serine levels in the brain.

"Casein kinase 1δ-IN-4 (compound 567) is a potent inhibitor of casein kinase 1δ with potential application in Alzheimer's disease research [1]."

Cholesterylamine, a cationic lipid, can be incorporated into PLGA to create particles with a charged surface, facilitating its use in drug delivery systems and

Anticancer agent 121, a human lactate dehydrogenase A (hLDHA) inhibitor, exhibits potent anticancer activities, suitable for use in anticancer research [1].

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.

PDE1-IN-2 is an PDE1 inhibitor(PDE1C, PDE1B and PDE1A with IC50 values of 6, 140 and 164 nM, respectvely).

1-Palmitoyl-2-lauroyl-sn-glycero-3-PC (1,2-PLPC) is a phospholipid with palmitoyl (16:0) and lauryl (12:0) acyl chains at the sn-1 and sn-2 positions, respectively. This mixed-chain phosphatidylcholine aids in researching the role of chain-chain contact interactions in maintaining the structural stability of lipid membrane bilayers.

244cis, an ionizable cationic lipid incorporating a piperazine structure, facilitates the creation of lipid nanoparticles (LNPs). These LNPs, when formulated with 244cis and coated with an mRNA reporter gene, exhibit preferential accumulation in the lungs of mice, in contrast to those formulated with SM-102. Additionally, it leads to a reduction in the levels of serum chemokine (C-C motif) ligand 2 (CCL2) [1].

GSK356278: selective PDE4A/B/D inhibitor, pIC50~8.7, anti-inflammatory, anxiolytic, cognition-enhancing.

2-Phenyl-2-(2-pyridyl)acetonitrile represents the principal metabolite of the antigastric agent SC 15396, produced by the supernatant fraction of rat liver

1-Linoleoyl-3-α-linolenoyl-rac-glycerol, a diacylglycerol, features linoleic acid at the sn-1 position and α-linolenic acid at the sn-3 position. This compound is identified in olive oil that has undergone lipase-catalyzed glycerolysis, utilizing immobilized lipase B derived from C. antarctica.

1,3-Dipalmitoyl-2-docosahexaenoyl glycerol, a triacylglycerol, features palmitic acid at the sn-1 and sn-3 positions and docosahexaenoic acid at the sn-2 position. Its dietary administration (30 g/kg) has been shown to decrease hepatic triglyceride and cholesterol levels in mice.

2-Stearoyl-sn-glycero-3-phosphatidylcholine (2-Stearoyl-sn-glycero-3-PC) is a lysophospholipid characterized by the presence of stearic acid at the sn-2 position. This compound has been identified in the myocardium of rabbits.

ICMT-IN-15 (compound 51) serves as an ICMT inhibitor with an IC50 value of 0.032 μM [1].

1,2-Dioleoyl-3-stearoyl-rac-glycerol, a triacylglycerol, features oleic acid at the sn-1 and sn-2 positions and stearic acid at the sn-3 position. This compound is present in sunflower, corn, and soybean oils, as well as in ostrich oil.

9(Z),11(E)-Conjugated Linoleic Acid Methyl Ester, identified in lemon grass (C. flexuosus), serves as a standard for quantifying conjugated linoleic acids in thermally stressed olive oil and trans fats in bakery products. [Matreya, LLC. Catalog No. 1255]

Leramistat is a mitochondrial complex I (NIC1) inhibitor that alters cellular metabolism and reduces proliferation in human primary lung fibroblasts.

(R)-Azasetron besylate (SENS-401), an orally active calcineurin inhibitor, has been shown to mitigate cisplatin-induced hearing loss and cochlear damage [1][2].

Amentoflavone hexaacetate is a 3,5-cyclic nucleotide phosphodiesterase inhibitor. It has anti-angiogenic and anti-metastatic effects.

AZD7687: Selective DGAT1 inhibitor, IC50 of 80 nM. In vitro reduces postprandial TAG. In vivo significant GI side effects at >5 mg/day dose.

1,3-Distearoyl-2-palmitoyl glycerol, a triacylglycerol, comprises stearic acid at the sn-1 and sn-3 positions, and palmitic acid at the sn-2 position. This compound is present in bovine milk fat.

11β-Prostaglandin F2αethanolamide (11β-PGF2α-EA), posited as the hepatic metabolite derived from PGD2-EA during COX-2 metabolism of AEA—an endogenous cannabinoid present in brain, liver, and various mammalian tissues—is synthesized directly from AEA via COX-2 and specific prostaglandin synthase, leading to ethanolamide versions of classical prostaglandins. Additionally, PGD2-EA formation occurs in activated RAW 264.7 cells upon AEA treatment.

1,3-Dipalmitoyl-2-stearoyl glycerol, a triacylglycerol, incorporates palmitic acid at the sn-1 and sn-3 positions and stearic acid at the sn-2 position. This compound's levels diminish in rats experiencing an energy deficit due to restricted food intake, in contrast to those in fed rats.

MK-8666, a partial GPCR agonist targeting GPR40, may treat type 2 diabetes by enhancing insulin secretion and lowering glucose safely.

12(Z),15(Z)-Heneicosadienoic acid, an ω-6 very long-chain polyunsaturated fatty acid, serves as a positional isomer of heneicosadienoic acid, which is scarcely found in living organisms.

Salbutamol (albuterol), a selective β2-adrenergic partial agonist, serves as a bronchodilator widely used in various clinical scenarios and to counteract doping abuse. Its process impurity, Albuterol methyl ether, may be present in urine samples, highlighting the importance of detection and chemical analysis.

1-Palmitoyl-2-arachidoyl-3-oleoyl-rac-glycerol, a triacylglycerol, incorporates palmitic acid, arachidic acid, and oleic acid at the sn-1, sn-2, and sn-3 positions, respectively, and is identified in cod liver oil.

CLB-016 is an inhibitor of hypoxia-inducible factor (HIF)-1.

1-Aminodecylidenebis-phosphonic acid, with its potent inhibitory effect on acid sphingomyelinase (IC50= 20 nM), shows selectivity by being less effective against neutral sphingomyelinase (IC50= >100 μM). Additionally, it entirely prevents dexamethasone-induced apoptosis in HepG2 cells.

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

Aladotril is an inhibitor of neutral endopeptidase. Its prodrug is aladotrilat.

YM17E is an inhibitor of ACAT with IC50 of 44 nM in rabbit liver microsomes in vitro.

ML395 is a potent, selective PLD2 allosteric inhibitor with potent antiviral activity (IC50 =360 nM).

Diflumidone sodium is a non-steroidal agent with anti-inflammatory activity.

H-0104 Dihydrochloride is an inhibitor of ROCK that acts by applying potent intraocular pressure (IOP)-lowering effects into the eyes of monkeys.

HIF-2α-IN-13 (18) acts as a HIF-2α inhibitor and exhibits an IC 50 value of 2.7 μM.

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.

A 62198 is a potent and selective renin inhibitor with potential as a hypotensive agent.

Aladotrilat is an inhibitor of neutral endopeptidase. Its prodrug is aladrotril.

11-Dehydro-2,3-Dinor Thromboxane B2 is a metabolite of Thromboxane B2 (TXB2), formed by the oxidation of TXB2 via 11-Hydroxy Thromboxane Dehydrogenase.

Tiracizine HCl, a new class I antiarrhythmic drug, was studied in patients with ischemic heart disease and shown to decrease myocardial contractile function.

Curcumin-β-D-glucuronide, a principal metabolite detected in hepatic tissue and portal blood following oral consumption of Curcumin, is utilized in colon cancer

ERX-41 is an orally active, stereospecific small molecule that targets lysosomal acid lipase A (LIPA).

PF-915275 inhibits 11βHSD1 in humans (Ki=2.3 nM, EC50=15 nM) and affects cortisone-cortisol conversion in hepatocytes.

MR-2-93-3, a long-chain fatty acid, functions as a carrier for polynucleotides [1].

Gisadenafil besylate (UK 369003-26) is a potent and orally active PDE5 inhibitor, for lower urinary tract symptoms associated with benign prostatic hyperplasia.

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.

ICMT-IN-10 (compound 32) serves as an inhibitor for ICMT, exhibiting potent activity with an IC50 value of 0.184 μM [1].

N-Formyl-L-histidine is a competitive inhibitor of L-histidine deaminase (Ki = 4.26 mM) and also binds to histidine-tRNA synthetase (Ki = 4.6 μM).

ICMT-IN-24 (compound 63) is an inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), exhibiting potent activity with an IC50 value of 0.19 μM [1].

(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].

SHP2-IN-20 (compound 193), a potent SHP2 inhibitor, exhibits an IC50 of 3 nM, making it suitable for glioblastoma research [1].

RORγt agonist 2 is a potent agonist of RORγt.

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

ICMT-IN-3 (Compound 27) serves as a potent inhibitor of ICMT, demonstrating an IC50 value of 0.015 μM [1].

ICMT-IN-41 (compound 20) serves as a potent inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), demonstrating an IC50 value of 0.069 μM [1].

5-PAHSA, a FAHFA formed through the formal condensation of the carboxy group of palmitic acid with the hydroxy group of 5-hydroxystearic acid, serves as a human metabolite, possesses anti-inflammatory and hypoglycemic properties, and is categorized as a long-chain fatty acid. This compound, deriving from hexadecanoic acid and octadecanoic acid, is the conjugate acid of a 5-PAHSA(1-).

Zofenoprilat, an angiotensin-converting enzyme (ACE; IC50 = 8 nM for rabbit lung enzyme) inhibitor and the active metabolite of the prodrug zofenopril,

1,2-Dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE), a phosphatidylethanolamine derivative featuring lauric acid (12:0) acyl chains, serves in the development of liposomes [1].

3-Decyl-5,5'-diphenyl-2-thioxo-4-imidazolidinone (compound 45), having a pI50 of 5.89, shows promise as an inhibitor of fatty acid amide hydrolase (FAAH). Despite its activity, it demonstrates a lack of affinity for cannabinoid receptors CB(1) and CB(2) [1].

(±)16,17-EDT, an oxylipin metabolite of adrenic acid produced through the cytochrome P450 (CYP) pathway, effectively induces dilation in isolated porcine

3-Aminoisobutyric acid, a non-protein amino acid resultant from thymine catabolism, plays a significant role in metabolic activities. At a 5 µM concentration, it triggers browning in primary adipocytes, notably elevating uncoupling protein 1 (UCP-1) and CIDEA expression. Additionally, it boosts PPARα expression in both primary adipocytes and mouse inguinal white adipose tissue (WAT) in vivo, alongside enhancing β-oxidation in hepatocytes. Its plasma levels surge post-exercise in mice, and its administration at 100 mg/kg daily curtails weight gain and body fat without diminishing food consumption or hiking energy output, whilst ameliorating glucose tolerance. Notably, 3-aminoisobutyric acid concentrations are heightened in individuals with β-ureidopropionase deficiency, a genetic flaw impairing pyrimidine degradation, affecting plasma, urine, and cerebrospinal fluid.

ICMT-IN-4 (compound 28) serves as an inhibitor of ICMT, exhibiting an IC50 value of 0.27 μM [1].

GIV3727, a bitter taste receptor hTAS2R antagonist, inhibits the activation of hTAS2R31 by saccharin and acesulfame potassium, effectively diminishing the

1,2-Dioleoyl-3-docosohexaenoyl-rac-glycerol, a triacylglycerol, consists of oleic acid at the sn-1 and sn-2 positions and docosahexaenoic acid at the sn-3 position. This compound has been identified in human breast milk.

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.

NOX2-IN-1 (compound 10) serves as an inhibitor of the enzyme nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2).

Sezolamide hydrochloride is a potent topical carbonic anhydrase inhibitor.

4-Hydroxyphenylglyoxylic acid, an active metabolite of the prodrug oxfenicine, functions as an inhibitor of carnitine palmitoyltransferase 1 (CPT1).