Metabolism

<p>11β-13,14-Dihydro-15-keto PGF2α, a PGD2 metabolite in the 15-hydroxy PGDH pathway, is formed in human males upon infusion or inhalation of tritiated PGD2, with peak plasma levels of both 11β-PGF2α and 11β-13,14-dihydro-15-keto PGF2α observed within 10 minutes. In human lung homogenates, PGD2 is metabolized firstly to 11β-PGF2α and subsequently to 11β-15-keto-PGF2α in the presence of NAD+, but not to 11β-13,14-dihydro-15-keto PGF2α. Conversely, guinea pig liver and kidney homogenates can metabolize PGD2 to 11β-13,14-dihydro-15-keto PGF2α via 11β-PGF2α, with both NAD+ and NADP+ being requisite for this conversion.</p>

<p>(R)-tert-OMe-byakangelicin, a furanocoumarin, exhibits inhibitory effects on liver drug metabolizing enzyme (DME) activity and can be isolated from the immature</p>

<p>α-Glucosidase-IN-29 (compound 19) is an inhibitor of α-glucosidases, exhibiting an IC50 value of 1.21 μM and a Ki of 1.80 μM.</p>

<p>A 79175 is a 5-lipoxygenase inhibitor that increases bone formation.</p>

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

<p>ICMT-IN-11 (compound 48) serves as an ICMT inhibitor with an IC50 value of 0.031 μM [1].</p>

<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>

<p>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].</p>

<p>N-Methyl Palbociclib is an impurity of the orally active selective CDK4 and CDK6 inhibitor Palbociclib (PD 0332991).</p>

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

<p>PF-04937319 activates glucokinase (EC50=154.4μM) with low hypoglycemia risk, researched for type 2 diabetes treatment.</p>

<p>ICMT-IN-22 (compound 62) acts as an ICMT inhibitor with an IC50 value of 0.63 μM [1].</p>

<p>(R)-Avanafil ((R)-TA1790) is a selective phosphodiesterase type 5 (PDE5) inhibitor with an IC50 of 5.2 nM, utilized for the research of erectile dysfunction [1</p>

<p>RORγt agonist 3 is a potent agonist of RORγt.</p>

<p>G43-C3-TEG is a glycosyl-transferase inhibitor that diminishes biofilm formation by inhibiting the synthesis of extracellular polysaccharides (EPS) [1].</p>

<p>Anticancer agent 122, a potent inhibitor of human lactate dehydrogenase A (h LDHA), exhibits significant anticancer activities, rendering it suitable for use in</p>

<p>CYP11A1-IN-1 (compound 30) is a selective inhibitor of the enzyme CYP11A1, displaying an IC50 ranging from 201-2000 nM.</p>

<p>PF-04957325 is an inhibitor of PDE8.PF-04957325 has an IC50 of 0.7 nM for PDE8A.PF-04957325 can be used for the study of autoimmune encephalomyelitis.</p>

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

<p>MS-444 (BE-34776) is an MLCK and HuR inhibitor with antitumor activity that can be used to study triple-negative breast cancer and colorectal cancer.</p>

<p>Quercetin 7-glucuronide (Quercetin 7-O-β-glucuronide), a Quercetin metabolite found in Madagascarian Uncarina species, has the capability to inhibit LDL</p>

<p>FTI-276 is an inhibitor of protein farnesyltransferase (PFT) (IC50s: 0.9 and 0.5 nM for Plasmodium falciparum and human).</p>

<p>ICMT-IN-40 (compound 19) is a potent inhibitor of ICMT, exhibiting an IC50 value of 0.031 μM [1].</p>

<p>L 670630 is a potent and orally active 5-lipoxygenase inhibitor.</p>

<p>Glucocerebrosidase-IN-1 (compound 11a) hydrochloride is a potent, selective GCase (glucocerebrosidase) inhibitor with IC50 and Ki values of 29.3 μM and 18.5 μM</p>

<p>Amb123203 is an inhibitor of the budding of mVP40 and eVP40 VLPs that acts by blocking mVP40-795 Nedd4 protein-protein interaction.</p>

<p>D-threo-PDMP inhibits glucoceramide synthase, cutting cell surface glycosphingolipids and hindering neurite growth.</p>

<p>PPARδ agonist 9 (compound 21), with an EC50 of 3.6 nM, is effective in vivo, decreasing serum MCP-1 concentrations in mice and markedly reducing atherosclerotic</p>

<p>Compound 144 (also known as Anticancer Agent 144) is a potent inhibitor of both PTPN2 and PTP1B, exhibiting IC50 values of less than 2.5 nM, making it suitable</p>

<p>BMS-186511: An FT inhibitor targeting malignant cells in NF1, halting growth and spread without affecting related enzymes.</p>

<p>"Lipid AX4, characterized as an ionizable cationic lipid with a pKa of 6.89, facilitates the formation of lipid nanoparticles (LNPs) for in vivo mRNA delivery [1]."</p>

<p>IDH1 Inhibitor 7 is an IDH1 inhibitor with an IC 50 of less than 100 nM .</p>

<p>cis-Clopidogrel-MP derivative, also Clopidogrel-MP-AM, is a 3'-methoxyacetophenone Clopidogrel metabolite and oral P2Y12 receptor platelet inhibitor.</p>

<p>AS 183 is an inhibitor of cholesterol acyltransferase (ACAT).</p>

<p>ICMT-IN-32 (compound 70) acts as an inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), demonstrating an IC50 value of 0.777 µM [1].</p>

<p>Glycolithocholic acid (Lithocholic acid glycine conjugate) is a glycine conjugate of lithocholic acid.</p>

<p>CP-113818 is a potent inhibitor of cholesterol acyltransferase (ACAT) and can be used to study Alzheimer's disease.</p>

<p>Dasatinib analog-1 (compound 5826) demonstrates inhibition of CYP3A4 activity, presenting a K_i value of 5.4 μM, and effectively prevents the formation of glutathione adducts [1].</p>

<p>FAAH Inhibitor 2 (Compound 17b) is an irreversible inhibitor of fatty acid amide hydrolase (FAAH), demonstrating an IC50 value of 0.153 μM [1].</p>

<p>M-0002, a vasopressin V2 receptor antagonist, is used potentially for the treatment of ascites.</p>

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

<p>4-Methylumbelliferyl-α-D-Glucopyranoside (4MU-αGlc) is a fluorescence substrate for α-glucosidase, serving as a biomarker for Fabry disease and Pompe disease</p>

<p>CHK-336 (Example 1), an orally active LDHA inhibitor (IC50 &lt;1 nM), suppresses lactate production in mouse hepatocytes and is applicable in hyperoxaluria</p>

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

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

<p>KRP-109, a neutrophil elastase (NE) inhibitor, acts by decreasing expression of TGF-ß Signal Related Genes.</p>

<p>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-).</p>

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

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

<p>DMPA, a derivative of phosphatidic acid (PA), constitutes a significant component of cellular membranes.</p>

<p>Ionizable Lipid-2 (Compound 1) serves as an ionizable lipid, essential for nucleic acid delivery and the construction of lipid nanoparticles (LNPs) [1].</p>

<p>Z-Pro-Pro-CHO acts as a prolyl oligopeptidase inhibitor with half-maximal inhibitory concentrations (IC50) of 0.16 μM for human prolyl oligopeptidase and 0.01</p>

<p>BMS-962212: reversible, selective FXIa blocker, well-tolerated, quick PD effect, rapid clearance, alters clotting time/activity.</p>

<p>GSK-8062 is an agonist of farnesoid X receptor (FXR).</p>

<p>SCD1/5-IN-1 (Compound 10), a selective SCD1/5 inhibitor, is utilized in the research of neurological diseases [1].</p>

<p>Sulforhodamine 101 DHPE, a fluorescent probe, results from the conjugation of sulforhodamine 101, a red fluorescent dye with excitation/emission spectra of 586/605 nm, to the phospholipid 1,2-dipalmitoyl-sn-glycero-3-PE. It effectively integrates into phospholipid bilayers and is utilized for imaging solid supported lipid bilayers, detecting protein-ligand interactions on bilayers, and monitoring lipid probe colocalization in liposomes through resonance energy transfer (RET).</p>

<p>ICMT-IN-51 (compound 43) serves as an ICMT inhibitor with an IC50 value of 0.55 μM [1].</p>

<p>H-0106 Dihydrochloride is an inhibitor of ROCK that acts by applying strong intraocular pressure (IOP)-lowering effects into the eyes of monkeys.</p>

<p>Glycosidase-IN-2 is a glycosidase inhibitor with hypoglycemic activity.</p>

<p>4BAB (compound 29) is an irreversible inhibitor of glyoxalase I (GLO1) and exhibits anticancer activity.</p>

<p>FAAH/cPLA2α-IN-1 is a compound that simultaneously inhibits both FAAH and cPLA2α, demonstrating potent activity with half-maximal inhibitory concentrations (</p>

<p>GSK2324 is a potent FXR agonist for the treatment of NAFLD by controlling hepatic lipids through reduced uptake and selective reduction of fatty acid synthesis.</p>

<p>AZD-1656 is a glucokinase activator (GKA) that can cause dose-limiting hypoglycemia in normal animals used in embryofetal development studies and type 2</p>

<p>"9322-O16B, an ionizable cationic lipid, facilitates the generation of lipid nanoparticles (LNPs) [1]."</p>

<p>AZD6605 is a potent, reversible inhibitor of, MMP2, MMP9, MMP12 and MMP13.</p>

<p>PPARγ agonist 8, a compound that acts on the peroxisome proliferator-activated receptor gamma (PPARγ), has been shown to stimulate peroxisome proliferator</p>

<p>GNE-783 is a selective inhibitor of CHK1.</p>

<p>Taurohyocholic acid (THCA), a taurine-conjugated form of porcine-specific primary bile acid hyocholic acid, inhibits cholesterol crystal precipitation by stabilizing cholesterol in the liquid-crystalline phase and prevents cholestasis and cellular necrosis in isolated rat livers induced by taurolithocholic acid. Additionally, THCA levels rise in the urine of patients with hepatitis B-induced cirrhosis.</p>

<p>JNJ-42259152 is a phosphodiesterase 10A PET tracer.</p>

<p>AS1468240 is a factor Xa inhibitor. It has significant oral anticoagulant activity.</p>

<p>Gentisuric acid, an Aspirin metabolite and a substrate of α-amidating monooxygenase (PAM), mitigates DNA damage induced by Mitomycin C. [1] [2]</p>

<p>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].</p>

<p>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].</p>

<p>BBT has anti-hyperglycemic activity, protecting beta cells from cytokine or streptozotocin-induced cell death, and restoring beta cell function.</p>

<p>TMDJ-035 is a selective inhibitor of the RyR2 (ryanodine receptor 2).</p>

<p>Aladotril is an inhibitor of neutral endopeptidase. Its prodrug is aladotrilat.</p>

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

<p>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.</p>

<p>3-Hydroxycarbofuran, a principal metabolite of Carbofuran, acts as a reversible inhibitor of acetylcholinesterase (AChE) [1].</p>

<p>GCase Modulator-1 (Compound 9g), a quinazoline derivative, functions as a glucosidase modulator with an AC50 value of 2.23 µM [1].</p>

<p>Cyclophellitol aziridine, an analogue of cyclophenol, serves as a potent inhibitor of β-glucosidase [1].</p>

<p>G1-OC2-K3-E10, an ionizable lipid, facilitates mRNA delivery through lipid nanoparticles (LNPs) [1].</p>

<p>Quizalofop-P, a selective herbicide, is absorbed by weed stems and leaves before translocating both upward and downward within the plant, concentrating in</p>

<p>11-Hexadecenoic acid, a monounsaturated fatty acid, comprises both 11-cis-hexadecenoic acid and 11-trans-hexadecenoic acid. These isoforms are present in ewe milk fat and their concentrations increase when the diet is supplemented with lipids from linseed, sunflower, olive, or fish oils. Additionally, 11-trans-hexadecenoic acid is found in intramuscular fat of both male and female foals. The product is a blend of the 11-cis and 11-trans forms. [Matreya, LLC. Catalog No. 1208]</p>

<p>Diflumidone sodium is a non-steroidal agent with anti-inflammatory activity.</p>

<p>Diethyl-pythiDC is an collagen prolyl 4-hydroxylase inhibitor.</p>

<p>Frunexian (EP-7041) is a selective and potent inhibitor of coagulation factor XI/activated factor XI, specifically targeting XIa.</p>

<p>RORγt inverse agonist 26, a potent reverse agonist of RORγt, effectively modulates Th17 cell differentiation and suppresses IL-17 production.</p>

<p>BMS641 (BMS-209641) is a RARβ agonist with affinity for RARβ that synergistically activates RARβ and RARgamma to induce cell maturation.</p>

<p>Lp-PLA2-IN-14 (Compound 19), an inhibitor of rhLp-PLA2, exhibits a potent inhibitory effect with a pIC50 value of 8.4.</p>

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

<p>LX-1031 is an effective inhibitor of tryptophan 5-hydroxylase. LX-1031 decreases serotonin (5-HT) synthesis peripherally.</p>

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

<p>CYP17-IN-1 is an effective oral inhibitor of CYP17 that can inhibit CYP17 in rats and humans with IC50 of 15.8 and 20.1 nM.</p>

<p>FASN-in-1 is an effective, specific inhibitor of fatty acid synthase (FASN), a compound specifically designed to target and inhibit the activity of the enzyme</p>

<p>Adibendan (Adibendanum) is a selective inhibitor of PDE3 with an IC50 of 2.0 μM.</p>

<p>6β-hydroxy Testosterone （4-Androsten-6β,17β-diol-3-one） is a 17β-hydroxy steroid, an androgen and endogenous metabolite.</p>

<p>PPAR agonist 1 is an agonist of PPAR α/γ, used for reducing blood glucose, lipid levels, reducing body weight, and lowering cholesterol.</p>

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

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