Metabolismo

<p>N-Acyl taurines, such as N-lignoceroyl taurine, alongside various arachidonoyl amino acid conjugates like N-arachidonoyl dopamine and N-arachidonoyl-L-serine, have been identified in bovine brain and through mass spectrometry lipidomic studies in the brain and spinal cord of both wild-type and FAAH knockout mice. Notably, N-lignoceroyl taurine levels were found to be 23-26 times higher in FAAH knockout mice than in wild types, suggesting its degradation by FAAH, despite in vitro evidence showing FAAH hydrolyzes N-lignoceroyl taurine significantly slower than oleoyl ethanolamide. Additionally, N-acyl taurines with polyunsaturated acyl chains are known to activate TRPV1 and TRPV4 channels within the transient receptor potential (TRP) family of calcium channels.</p>

<p>5(S)-HETrE, made by 5-LO from mead acid, has unknown biological activity and metabolic fate.</p>

<p>UK-157147 is a substrate for UGT1A1(Km: 105 μM).</p>

<p>UK 357903, a phosphodiesterase 5A (PDE5A) inhibitor, is used potentially for the treatment of erectile dysfunction.</p>

<p>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.</p>

<p>11-Dehydro Thromboxane B3 (11-dehydro TXB3) serves as a urinary metabolite of TXA3 in humans following an increased dietary intake of EPA.</p>

<p>9(Z),11(Z)-Octadecadienoic acid, an isomer of linoleic acid, demonstrates antitumor activity with an EC50 value of 446.1 µM [1].</p>

<p>JTV-803 inhibits factor Xa (K(i) 0.019 µM, IC(50) 0.081 µM), 100x more selective vs thrombin, extends clotting times dose-dependently.</p>

<p>S-Fcme activates multidrug resistance transporter by boosting ATPase activity and competing for drug binding.</p>

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

<p>KD-026 (SLx 4090), a microsomal triglyceride transfer protein (MTP) inhibitor(IC50 = 8.0 nM), is used in type 2 diabetes studies.</p>

<p>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</p>

<p>FAS-IN-1 Tosylate is an effective fatty acid synthase inhibitor;Has an IC50 of 10 nM.</p>

<p>Glycosidase-IN-1, a D-mannose-derived inhibitor, has hypoglycemic effects and aids in creating immunosuppressants and β-glucosidase blockers.</p>

<p>GSK2647544 inhibits Lp-PLA2, a pro-inflammatory enzyme from macrophages, orally active, calcium-independent.</p>

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

<p>A 62198 is a potent and selective renin inhibitor with potential as a hypotensive agent.</p>

<p>hCAIX-IN-16 (Compound 12d), an inhibitor of hCA IX, exhibits inhibition constants (K i) of 190.0 nM for hCA IX and 187.9 nM for hCA XII.</p>

<p>Miglustat hydrochloride (N-Butyldeoxynojirimycin hydrochloride) is an inhibitor of glucosylceramide synthase and can be used for studies about Type I Gaucher</p>

<p>glycogen phosphorylase inhibitor</p>

<p>II-B08 is a cell-permeable SHP2 inhibitor (IC50 = 5.5 µM). II-B08 blocks growth factor stimulated ERK1/2 activation and hematopoietic progenitor proliferation.</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>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>E-5324 is potent cholesterol acyltransferase (ACAT) inhibitor (IC50s: 44 to 190 nM).</p>

<p>Tetrahydro-11-dehydrocorticosterone is an inhibitor of 11β-hydroxysteroid dehydrogenase [1].</p>

<p>Efipladib is a phospholipase inhibitor. Efipladib decreases nociceptive responses without affecting PGE2 levels in the cerebral spinal fluid.</p>

<p>ICMT-IN-46 (compound 25) is a potent inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), exhibiting an IC50 value of 0.556 μM [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>hCAIX/XII-IN-8 (compound 3g) is a potent inhibitor of the human carbonic anhydrases (CAs) IX and XII, with inhibition constants (K i) of 8.5 nM for CA IX and 6.</p>

<p>ICMT-IN-17 (compound 52) serves as an ICMT inhibitor, exhibiting an IC50 value of 0.38 μM [1].</p>

<p>VU0364739, a selective phospholipase D2 (PLD2) inhibitor with an IC50 of 22 nM, effectively reduces cancer cell proliferation [1].</p>

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

<p>ICMT-IN-5 (compound 46) is an ICMT inhibitor with an IC50 value of 0.3 μM [1].</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>GGTI-2133: potent GGTase I inhibitor, IC50=38 nM; blocks inflammatory cell invasion in mice asthma.</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>ICMT-IN-1 (compound 75) is a potent ICMT inhibitor with an IC50 value of 0.0013 μM.</p>

<p>Zopolrestat (CP 73850) is a potent inhibitor of aldose reductase (IC50 = 3.1 nM).</p>

<p>RORγt Inverse agonist 6 is an agonist of RORγt inverse. RORγt Inverse agonist 6 can be used in research on Th17-driven autoimmune diseases.</p>

<p>8-Hydroxyguanine, generated through the oxidative degradation of DNA by the hydroxyl radical, serves as an indicator of oxidative stress in biological systems.</p>

<p>S-Benzylglutathione acts as a competitive inhibitor of glutathionase and undergoes conversion by rat kidney microsomes into its cysteine derivatives.</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>Aladotrilat is an inhibitor of neutral endopeptidase. Its prodrug is aladrotril.</p>

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

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

<p>Fasidotril inhibits NEP/ACE, treats high blood pressure in rats, effective in humans with hypertension.</p>

<p>AalphaC (2-Amino-alpha-carboline) is a potential carcinogen.</p>

<p>MSI-1436 is a selective, non-competitive the enzyme protein-tyrosine phosphatase 1B (PTB1B)inhibitor(IC50 of appr 1 μM)</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>RP 70676 is a potent ACAT inhibitor(rat and rabbit ACAT with IC50 of 25 and 44 nM ).</p>

<p>Ilepatril, also known as AVE-7688, is a vasopeptidase inhibitor for the treatment of hypertension.</p>

<p>DORI, a cationic lipid, efficiently delivers plasmid DNA in vitro, exhibiting lower cytotoxicity and high transfection efficiency [1].</p>

<p>Implitapide Racemate is the racemate of Implitapide. Implitapide is an inhibitor of microsomal triglyceride transfer protein (MTP).</p>

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

<p>Prostaglandin F2α-1-glyceryl ester undergoes oxidation via 15-hydroxyprostaglandin dehydrogenase (15-HPGDH) [1].</p>

<p>WT IDH1 Inhibitor 2 blocks wild-type and R132H mutant IDH1 (IC50: 120 nM); related to GSK321.</p>

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

<p>cKK-E15, a peptide-lipid, is instrumental in formulating LNP3 alongside C14PEG2000, unmodified cholesterol, and DOPE [1].</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>GW-6604 is an ALK5 inhibitor and shows clear antifibrotic effects resulting in liver function improvement.</p>

<p>FXIa-IN-7 is an orally available, selective and potent inhibitor of factor XIa for the study of thrombophilia.</p>

<p>MetAP2-IN-1 is a selective inhibitor of MetAP2, a target involved in angiogenesis-related conditions, suitable for research applications [1].</p>

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

<p>1,2-Dilinoleoyl-sn-glycero-3-PC (Dilinoleoyllecithin), a phospholipid, finds application in the production of artificial membranes [1].</p>

<p>VU0155069 hydrochloride (CAY10593 hydrochloride) is a potent and selective inhibitor of phospholipase D (PLD), exhibiting IC50 values of 46 nM for PLD1 and 933 nM for PLD2. It effectively inhibits the migration of both human and mouse breast cancer cell lines [1] [2].</p>

<p>α-Glucosidase-IN-28 (Compound 18) is an α-glucosidase inhibitor with an IC50 of 0.62 μM and Ki value of 3.93 μM.</p>

<p>C2 Dihydro Ceramide (d18:0/2:0) (C2 Dihydroceramide) is a ceramide that is a precursor of ceramide synthesis and stimulates ABCA1-mediated cholesterol efflux.</p>

<p>5-Lipoxygenase-In-1 (compound example 4.10) is a 5-Lipoxygenase inhibitor.</p>

<p>Niraxostat (Y-700) is one of the isocytosine derivatives as xanthine oxidase inhibitors.</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>SHP2-IN-19 (compound 183) is a SHP2 inhibitor exhibiting potent activity with an IC50 of 3 nM, and is utilized in glioblastoma research [1].</p>

<p>15-PGDH-IN-1: potent oral 15-PGDH inhibitor, IC50=3nM, useful for tissue repair research.</p>

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

<p>Tisolagiline (KDS2010) is a potent, highly selective and reversible MAO-B inhibitor oral activity for the treatment of Alzheimer's disease and obesity.</p>

<p>TMP778 is an effective and selective RORγt inverse agonist (IC50: 7 nM in FRET assay).</p>

<p>(±)-HIP-A is an excitatory amino acid transporter blocker.</p>

<p>Bucolome (Paramidine) is a CYP2C9 inhibitor with uricosuric and anti-inflammatory activity.</p>

<p>Celgosivir (6 O-butanoyl castanospermine) is an inhibitor of α-glucosidase I. In vitro assay, it inhibits bovine viral diarrhoea virus (BVDV) ( IC50: 1.27 μM ).</p>

<p>Nampt-IN-10 TFA, a NAMPT inhibitor, shows potency in A2780 (IC50: 5 nM) and CORL23 (IC50: 19 nM), suitable for ADC payloads.</p>

<p>NC1 is a potent allosteric inhibitor of lymphoid-specific PTPN22, a protein tyrosine phosphatase.</p>

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

<p>ICMT-IN-14 (compound 50) serves as an inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), exhibiting potent activity with an IC50 of 0.025 μM [1].</p>

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

<p>IDH1 Inhibitor 5 targets MOG cells (IC50: 64.4 nM) and R132H mutant IDH1 gliomas (IC50: 34.9 nM).</p>

<p>NUCC-0223619 is an IDO1 inhibitor that induces the degradation of IDO protein and can be involved in the synthesis of PROTAC.</p>

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

<p>Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are lipids that are modulated by dietary changes such as fasting and high-fat diets, and they play a role in insulin sensitivity. These compounds generally consist of a fatty acid chain of either 16 or 18 carbons (for example, palmitoleic, palmitic, oleic, or stearic acid) esterified to a similarly long hydroxy fatty acid. One specific FAHFA, 9-SAHSA, features stearic acid esterified at the 9th carbon of hydroxy stearic acid. The concentration of 9-SAHSA is notably increased in the serum of glucose-tolerant AG4OX mice, which specifically express the Glut4 glucose-transporting protein in adipose tissue.</p>

<p>PTP1B-IN-20: Selective PTP1B inhibitor, IC50=1.05μM; less effective on TCPTP (IC50=78μM), targets type 2 diabetes.</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-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.</p>

<p>inhibitor of both glial and neuronal uptake of glutamate, aspartate and cysteate.</p>

<p>MGAT2-IN-2 is a potent inhibitor of acyl CoA:monoacylglycerol acyltransferase 2 (MGAT2) (IC50 of 3.4 nM).</p>

<p>sEH/AChE-IN-4-15 is a dual sEH and AChE inhibitor crossing the BBB, with IC50s: 3.1 nM (hsEH), 1660 nM (hAChE), 179 nM (hBChE), 14.5 nM (msEH), 102 nM (mAChE).</p>

<p>ICMT-IN-49 (Compound 2) acts as an ICMT inhibitor with an IC50 value of 0.12 μM [1].</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>Hypusine is an N-terminal amino alcohol derivative of Lys occurring in bovine brain &amp;</p>

<p>Bemfivastatin hemicalcium (PPD 10558), an orally active HMG-CoA reductase inhibitor, serves as a lipid-lowering agent.</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>Autotaxin-IN-5 is an Autotaxin inhibitor. It has the potential to treat idiopathic pulmonary fibrosis.</p>