Metabolism

<p>(R)-IDO/TDO-IN-1 (compound 25), an indoleamine-2,3-dioxygenase (IDO) inhibitor, demonstrates good pharmacokinetic properties and exerts anti-tumor effects in the MC38 xenograft model. This compound exhibits synergy when combined with the anti-PD-1 monoclonal antibody (SHR-1210) [1].</p>

<p>CRX000227 is a PPAR modulator suitable for researching metabolic and cell proliferative disorders [1].</p>

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

<p>Arachidonoyl amide (AMC-AA) is a fatty acid amide among several that serve to quantify fatty acid amide hydrolase (FAAH) activity. FAAH, with its relative lack of selectivity, processes various amide head groups beyond ethanolamine, the head group of its primary endogenous substrate, anandamide (AEA). The interaction of AMC-AA with FAAH leads to the liberation of fluorescent aminomethyl coumarin, which has an absorption peak at 360 nm and emission at 465 nm. This fluorescence release facilitates the rapid and efficient assessment of FAAH activity through the utilization of either a standard cuvette or a microplate fluorometer.</p>

<p>12(R)-HEPE, a monohydroxy fatty acid derived from EPA in the eggs of the sea urchin S. purpuratus, has a biological activity that, while not extensively documented, may resemble that of 12(R)-HETE (Catalog No.34560).</p>

<p>GW-6604 is an ALK5 inhibitor and shows clear antifibrotic effects resulting in liver function improvement.</p>

<p>GNE-6468 is a potent and selective agonist of RORγ(RORc) (EC50: 13 nM for HEK-293 cell).</p>

<p>PPACK: synthetic peptide, irreversibly inhibits thrombin (Ki = 0.24 nM), prevents platelet activation.</p>

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

<p>CAXII-IN-1, antitumor, selectively inhibits CA XII with Ki of 3.8 nM for hCA XII and 56 nM for hCA IX.</p>

<p>CJ-463, a selective uPA blocker, shows strong anti-tumor effect, especially at 100mg/kg, potentially treating lung cancer.</p>

<p>AZD1092 is the glucokinase enzyme activator.</p>

<p>Eucalyptacid A, a metabolite with antifungal properties, demonstrates efficacy against Alternaria solani, displaying minimum inhibitory concentrations (MIC)</p>

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

<p>Sch59498 is a potent phosphodiesterase 1c (Pde1c) inhibitor.</p>

<p>Yonkenafil, a PDE5 inhibitor, may reduce stroke damage and aid in Alzheimer's treatment.</p>

<p>FR-234938 is a non-nucleoside adenosine deaminase inhibitor with anti-inflammatory activity.</p>

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

<p>Cholesterol 24-hydroxylase-IN-2 is a potent inhibitor of cholesterol 24-hydroxylase (CH24H or CYP46A1), exhibiting an IC50 value of 5.4 nM, and has potential</p>

<p>PDE12-IN-3 is an inhibitor of phosphodiesterase 12 (PDE12) (pXC50 of 7.68),with antiviral activity.</p>

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

<p>Clocortolone pivalate, a synthetic steroid, treats dermatitis and psoriasis.</p>

<p>DLPA is a phosphatidic acid (PA) that incorporates the medium-chain lauric acid (12:0).</p>

<p>1,3-Dipalmitoyl glycero-2-phosphatidylethanolamine is a phospholipid incorporating saturated long-chain (16:0) stearic acid at the sn-1 and sn-3 positions, with phosphatidylethanolamine (PE) at the sn-2 position. Phosphatidylethanolamines, critical components of biological membranes, play essential structural and functional roles. Various PE types are instrumental in forming micelles, liposomes, and other synthetic membranes.</p>

<p>Difamilast is a selective inhibitor of phosphodiesterase-4 (PDE4) with particularly efficient inhibition of subtype B (IC50=11.2 nM).</p>

<p>9(Z),11(E),13(Z)-Octadecatrienoic acid methyl ester, an isomer of 9(Z),11(E),13(E)-octadecatrienoic acid methyl ester and the methyl ester derivative of 9(Z),11(E),13(Z)-octadecatrienoic acid, serves as a standard for quantifying 9(Z),11(E),13(Z)-octadecatrienoic acid in wild growing pomegranate (P. granatum) seed oil [Matreya, LLC. Catalog No. 1240].</p>

<p>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.</p>

<p>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.</p>

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

<p>RORγt modulator 4 is a RORγt modulator that regulates IL-17A production activity in cells derived from mouse spleen.</p>

<p>5α-Androst-16-en-3-one, a mammalian pheromone present in boar saliva, plays a crucial role in facilitating social and sexual interactions by acting as a volatile chemical cue. It is utilized to prime sows in estrus for mating or artificial insemination, underscoring its significance in reproductive behavior. Additionally, this compound is detected in human sweat and urine, where it is involved in studies concerning receptor-mediated odorant detection and the genetic foundations of anosmias, thereby broadening its scope of relevance beyond the animal kingdom.</p>

<p>CMI-392 is a dual 5-lipoxygenase inhibitor and platelet-activating factor (PAF) receptor antagonist (IC50s: 100 and 10 nM).</p>

<p>DSTAP chloride (CDESA), a cationic lipid, is utilized in the formation of lipid nanoparticles (LNPs) and exhibits high transfection efficiency [1].</p>

<p>ICMT-IN-29, also known as compound 66, effectively inhibits ICMT with an IC50 value of 0.019 μM [1].</p>

<p>First potent oral dual IDO1/IDO2 inhibitor with antitumor properties; IC50: 28 nM (IDO1), 144 nM (IDO2).</p>

<p>EMT inhibitor-2 blocks CYP3A4 and CYP2C9 (IC50: 49.72, 5.54 μM) and prevents IL-1β/TGF-β-induced EMT.</p>

<p>Compound 105 (h15-LOX-2 inhibitor 1) is a potent inhibitor of human epithelial 15-lipoxygenase-2 (h15-LOX-2), exhibiting an IC50 of 0.34 μM [1].</p>

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

<p>IDH1 Inhibitor 3 is a mutant isocitric dehydrogenase 1 (IDH1) inhibitor (IC50: 45 nM for IDH1R132H).</p>

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

<p>γ-CEHC, a metabolite of γ-tocopherol, is predominantly excreted through urine, primarily in its conjugated form as glucuronide [1], rather than through bile.</p>

<p>ICMT-IN-7 (compound 74), with an IC50 value of 0.015 µM, functions as an ICMT inhibitor, promotes cytoplasmic accumulation of ICMT in HCT-116 cells in a dose-</p>

<p>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.</p>

<p>Bemoradan is an inhibitor of the rolipram-insensitive cyclic AMP phosphodiesterase from canine heart tissue</p>

<p>Prostaglandin B2 is a dehydration product of PGE2/PGA2 with weak TP receptor activity, raising rabbit pulmonary pressure at &gt;5 ug/kg.</p>

<p>Desacetyl bisacodyl, the active metabolite of the laxative bisacodyl, evokes epithelial Cl(-) secretion in the rat colon and rectum, in addition to increasing</p>

<p>PHD2-IN-1, a potent and orally active HIF prolyl hydroxylase 2 (PHD2) inhibitor, exhibits an IC50 of 22.53 nM and is applicable in anemia research [1].</p>

<p>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].</p>

<p>MSI-1436 is a selective, non-competitive the enzyme protein-tyrosine phosphatase 1B (PTB1B)inhibitor(IC50 of appr 1 μM)</p>

<p>NOX2-IN-2 (compound 33) is a potent inhibitor of NOX2, disrupting the p47phox-p22phox protein-protein interaction with a dissociation constant (K i) of 0.24 μM.</p>

<p>Mitochondria degrader-1, a potent autophagy inducer, aids in neurodegenerative, cancer, and aging disease research.</p>

<p>SMS1-IN-1 is a potent inhibitor of sphingomyelin synthase 1 (SMS1, IC50 = 2.1 μM), and can be used in the atherosclerosis studies.</p>

<p>Oseltamivir acid methyl ester, a CES1-convertible neuraminidase inhibitor, serves as an antiviral prodrug.</p>

<p>15-PGDH-IN-2 (Compound 2) is an inhibitor of 15-PGDH with an IC50 value of 0.274 nM. This compound is useful for research into hair loss, bone formation, gastric ulcer healing, and dermal wound healing [1].</p>

<p>1-Stearoyl-2-hydroxy-sn-glycero-3-PG, a lysophospholipid characterized by the presence of stearic acid (18:0) at the sn-1 position, finds application in the creation of micelles, liposomes, and various artificial membranes, including those utilized in lipid-based drug delivery systems.</p>

<p>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.</p>

<p>GSK321 is an IDH1 inhibitor that prevents cytoplasmic glutamine reductive carboxylation.GSK321 is used in the study of leukemia.</p>

<p>DOG-IM4 is a chemical compound instrumental in synthesizing nanoparticles for delivering antigen-encoding nucleic acids, targeting a broad range of conditions including autoimmune diseases, rare blood or metabolic disorders, allergies, cancer, and infectious diseases [1].</p>

<p>C12-113, a lipidoid delivery agent, effectively transfects siRNA into cells and, when combined with additional lipids, forms lipid nanoparticles (LNPs). These LNPs facilitate the delivery of mRNA encoding the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice [1] [2].</p>

<p>Imiglitazar (TAK559) is a potent PPAR-β/δ receptor agonist with hypoglycemic effects.</p>

<p>"Oral FXR antagonist 1 selectively blocks intestinal FXR, with IC50 of 2.1 μM, aiding in NASH research by improving liver health."</p>

<p>ICMT-IN-8 (compound 30) serves as an inhibitor of ICMT, exhibiting an IC50 value of 0.652 μM [1].</p>

<p>Raloxifene Bismethyl Ether hydrochloride is a Raloxifene metabolite and an estrogen receptor inactive compound on which both hydroxyl groups are absent.</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>BMS-962212: reversible, selective FXIa blocker, well-tolerated, quick PD effect, rapid clearance, alters clotting time/activity.</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-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>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>C82 acts as an inhibitor of Mycobacterium tuberculosis (Mtb) cyclic dinucleotide phosphodiesterase (CdnP), with an IC50 value of 17.5 µM. This particular enzyme is responsible for breaking down cyclic di-AMP (c-di-AMP) into adenosine 5'-monophosphate (AMP). Notably, C82 demonstrates selectivity for Mtb CdnP over other bacterial cyclic dinucleotide phosphodiesterases (CDN PDEs) such as Yybt, RocR, and Group B Streptococcus (GBS) CdnP, as well as the mammalian CDN PDE ENPP1, and the viral CDN PDE poxin, showing effectiveness at a concentration of 200 µM.</p>

<p>Oxalomalic acid (Oxalomalate) trisodium, an inhibitor of aconitase and NADP-dependent isocitrate dehydrogenase, suppresses nitrite production and inducible nitric oxide synthase (iNOS) protein expression in lipopolysaccharide-activated J774 macrophages [1].</p>

<p>PHD-IN-2 (Compound 91), a potent PHD antagonist with an IC50 of less than 5 nM, effectively stimulates erythropoietin synthesis in HEP3B cells with an EC50 of</p>

<p>Selenocystine, a broad-spectrum anticancer agent, effectively induces DNA damage, notably DNA double-strand breaks (DSBs), in HepG2 cells, showcasing</p>

<p>HSD17B13-IN-3 (compound 2) is a potent inhibitor of hydroxysteroid 17ß-dehydrogenase 13 (HSD17B13), lacking cellular experimental activity [1].</p>

<p>1-Deazaadenosine, an adenosine deaminase inhibitor (Ki: 0.66 μM), may treat cancer, particularly lymphoproliferative disorders.</p>

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

<p>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.</p>

<p>RXPA 380: C-terminal ACE inhibitor, Ki=3nM; IC50=2.5nM for C-domain ACE mutants.</p>

<p>ICMT-IN-20 (compound 54) serves as an ICMT inhibitor with an IC50 value of 0.682 μM [1].</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>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>Quetiapine sulfoxide hydrochloride is a main metabolite of Quetiapinem. Quetiapine is a 5-HT receptors agonist and a dopamine receptor antagonist.</p>

<p>1-Oleoyl-2-hydroxy-sn-glycero-3-PG (sodium salt), a lysophospholipid with oleic acid (18:1) at the sn-1 position, finds application in creating micelles, liposomes, and various artificial membranes, notably in lipid-based drug delivery systems.</p>

<p>MLS000545091 is a potent and selective human epithelial 15-lipoxygenase-2 mixed-type inhibitor.</p>

<p>C24:1 1-Deoxyceramide (m18:1/24:1(15Z)) is a lipid molecule that can be used in life science related research. The CAS number of C24:1 1-Deoxyceramide (m18:1/24:1(15Z)) is 1246298-58-7.</p>

<p>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.</p>

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

<p>VULM 1457 is a potent ACAT inhibitor.</p>

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

<p>RORγt agonist 2 is a potent agonist of RORγt.</p>

<p>PD 109488 is a metabolite of quinapril and is a derivative of Quinapril that acts as an ACE inhibitor.</p>

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

<p>(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].</p>

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

<p>LY-338979 is an impurity of pemetrexedone.</p>

<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>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>Edaglitazone (R-483) is a PPARγ agonist with antiplatelet activity that can be used in studies of diabetes and obesity.</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>Lateritin (Bassiatin) is An Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor and a platelet aggregation inhibitor from the mycelial cake of Gibberella</p>

<p>17(S)-HpDHA, primarily produced by the 15-Lipoxygenase (LOX) isoenzymes h15-LOX-1 and h15-LOX-2 from docosahexaenoic acid (DHA), is a key regulator in epoxide synthesis through allosteric modulation. Additionally, it effectively inhibits platelet aggregation, demonstrating an EC50 of approximately 1 μM [1].</p>