Metabolism

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

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

<p>Entacapone acid (AG 1290) is a selective and reversible inhibitor of catechol-O-methyltransferase(COMT).</p>

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

<p>PTP1B-IN-20: Selective PTP1B inhibitor, IC50=1.05μM; less effective on TCPTP (IC50=78μM), targets type 2 diabetes.</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>JNJ-10258859 is a potent, and selective phosphodiesterase type 5 inhibitor with a K(i) of 0.23 nM.</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>BAY-7081 is a cyanopyridone-based compound that functions as a potent, selective, and orally active PDE9A inhibitor, demonstrating an inhibition concentration (</p>

<p>GPX4-IN-4 (Compound 24) serves as a potent inhibitor of GPX4, applicable in cancer research [1].</p>

<p>HIF-2α-IN-6 (117) is a HIF-2α inhibitor [1].</p>

<p>h-NTPDase-IN-5 (compound 3b) serves as a pan-inhibitor of NTPDase, exhibiting inhibitory concentration 50 (IC50) values of 1.10 μM (h-NTPDase1), 44.73 μM (h-</p>

<p>Mal-Pc, a maleimide phthalocyanine, depletes GSH to reduce aggregation and boost ROS, improving PDT against cancer.</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>VT-1598 tosylate is a selective, orally active antifungal compound that targets CYP51. It demonstrates efficacy against C. auris.</p>

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

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

<p>ICMT-IN-19 (compound 53) serves as a potent inhibitor of ICMT, demonstrating an IC50 value of 0.026 μM [1].</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-46 (compound 25) is a potent inhibitor of isoprenylcysteine carboxyl methyltransferase (ICMT), exhibiting an IC50 value of 0.556 μM [1].</p>

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

<p>CL4H6, a pH-sensitive cationic lipid, serves as the primary constituent of lipid nanoparticles (LNPs). These LNPs are instrumental in targeting and delivering siRNA, leading to a potent gene-silencing response [1] [2].</p>

<p>CYP3A4-IN-2, a potent CYP3A4 inhibitor (IC50: 0.055 μM), is a hydrophobic ritonavir analog with immunosuppressive and antiviral properties.</p>

<p>ICMT-IN-18 (compound 35) serves as an ICMT inhibitor with an IC50 value of 0.066 μM [1].</p>

<p>XL041 (BMS-852927) is an agonist of LXRβ-selective.</p>

<p>1-Palmitoyl-2-oleoyl-sn-glycero-3-PA (1,2-POPA) is a phospholipid featuring a palmitic acid (16:0) chain that is saturated and an oleic acid (18:1) chain that is monounsaturated, positioned at the sn-1 and sn-2 locations, respectively. This compound is utilized in creating micelles, liposomes, and various artificial membrane forms.</p>

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

<p>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.</p>

<p>hCAIX-IN-15 is a potent inhibitor of human carbonic anhydrase IX (hCA IX) with an inhibition constant (Ki) of 38.8 nM, exhibiting broad-spectrum anticancer</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>MMV009085 is a potent inhibitor of the Plasmodium falciparum hexose transporter (Pf HT1), with potential as an anti-malarial agent.</p>

<p>ICMT-IN-39, also known as compound 18, functions as an inhibitor of ICMT with an IC50 value of 0.031 µM [1].</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>Lp-PLA2-IN-2 is a selective and potent lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, with an IC50 0f 120 nM for recombinant human Lp-PLA2.</p>

<p>Cav 3.2 Inhibitor 4 (Compound 21) is a selective and potent inhibitor of the T-type calcium channel (Ca v 3.2), demonstrating peripheral restriction with an</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>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>FXIa-IN-1 is a potent β-lactam covalent heparin-derived factor XIa (fXIa) inhibitor.</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>Darglitazone (CP-86325) is a potent, selective agonist of PPAR-γ with antidiabetic actions.</p>

<p>3-Hydroxycarbofuran, a principal metabolite of Carbofuran, acts as a reversible inhibitor of acetylcholinesterase (AChE) [1].</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>KRP-109, a neutrophil elastase (NE) inhibitor, acts by decreasing expression of TGF-ß Signal Related Genes.</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>Frunexian (EP-7041) is a selective and potent inhibitor of coagulation factor XI/activated factor XI, specifically targeting XIa.</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>ICMT-IN-9 (compound 47) is a potent ICMT inhibitor with an IC50 value of 0.16 μM [1].</p>

<p>FTI-2153 inhibits farnesyltransferase with 1.4 nM IC50, &gt;3000x more effective on H-Ras than Rap1A.</p>

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

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

<p>Brodimoprim is an inhibitor of dihydrofolate reductase(DHFR).</p>

<p>5-Lipoxygenase-In-1 (compound example 4.10) is a 5-Lipoxygenase inhibitor.</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>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.</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>Ac-VDVAD-CHO is an inhibitor of caspase-2 and caspase-3 (IC50: 46 nM for caspase-2 and 15 nM for caspase-3) [1].</p>

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

<p>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.</p>

<p>BMS-262084 is a potent selective β-lactam trypsin inhibitor with therapeutic potential in the treatment of asthma.</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>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-30 (compound 67) is an ICMT inhibitor with an IC50 value of 0.27 μM [1].</p>

<p>1,2-Diheptadecanoyl-sn-glycero-3-phosphorylcholine (DHPC) is a derivative of phosphatidylcholine (PC) that exhibits biological activity, functioning as a</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>"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>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>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>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>Pactimibe is a ACAT inhibitor. It has anti-atherosclerotic activity.</p>

<p>ICMT-IN-45 (compound 24) serves as an ICMT inhibitor, demonstrating an IC50 value of 0.132 μM [1].</p>

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

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

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

<p>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.</p>

<p>SR11237 is a Pan retinoid X receptor (RXR) agonist.</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>First potent oral dual IDO1/IDO2 inhibitor with antitumor properties; IC50: 28 nM (IDO1), 144 nM (IDO2).</p>

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

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

<p>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].</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>Compound 22g: potent GLO1 inhibitor; IC50=0.011 μM; potential for depression, anxiety research.</p>

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

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

<p>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.</p>

<p>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.</p>

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

<p>KH064 is a sPLA2-IIA inhibitor of oral activity.</p>

<p>GNE-618 is a potent and orally active inhibitor of nicotinamide phosphoribosyltransferase (IC50: 6 nM).</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>