Metabolismo

<p>ICMT-IN-49 (Compound 2) acts as an ICMT inhibitor with an IC50 value of 0.12 μM [1].</p>

<p>PDP-EA is an activator of fatty acid amide hydrolase(FAAH) and enhances the amidohydrolase activity of FAAH.</p>

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

<p>IDO1/TDO-IN-6 (compound 11) is a dual inhibitor targeting IDO1 and TDO, exhibiting IC50 values of 2.25 μM for IDO1 and 2.89 μM for TDO.</p>

<p>PHD-IN-1 (compound 80) serves as a potent PHD2 inhibitor, exhibiting an IC50 value of ≤5 nM.</p>

<p>1-Isopropyltryptophan (1-IsoPT), an IDO1 inhibitor, suppresses the expression of IDO-1 and IDO-2 mRNA induced by IFN-γ stimulation [1].</p>

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

<p>BMS-986172 is an orally active, highly selective inhibitor of MGAT2, demonstrating inhibitory concentrations (IC50) of 4.6 nM for human MGAT2 (hMGAT2) and 20 nM</p>

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

GSK2973980A is a selective Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) inhibitor (IC50: 3 nM).

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>Perindopril acyl-β-D-glucuronide is a metabolite of the ACE inhibitor perindopril [1].</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>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>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>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>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>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>Gisadenafil besylate (UK 369003-26) is a potent and orally active PDE5 inhibitor, for lower urinary tract symptoms associated with benign prostatic hyperplasia.</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>BIO-32546 (S-isomer) is a highly potent regulator of autotaxin (ATX) with an IC50 value of 1 nM.</p>

<p>PF-915275 inhibits 11βHSD1 in humans (Ki=2.3 nM, EC50=15 nM) and affects cortisone-cortisol conversion in hepatocytes.</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>AalphaC (2-Amino-alpha-carboline) is a potential carcinogen.</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>Aladotrilat is an inhibitor of neutral endopeptidase. Its prodrug is aladrotril.</p>

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

<p>DPM-1001 is an orally bioavailable and non-competitive protein-tyrosine phosphatase (PTP1B) inhibitor (IC50: 100 nM) with the anti-diabetic property.</p>

<p>S-Fcme activates multidrug resistance transporter by boosting ATPase activity and competing for drug binding.</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>Iomazenil is an antagonist and partial inverse agonist of benzodiazepine and potential therapy for alcohol abuse.</p>

<p>Kelatorphan is an enkephalin degrading enzyme full inhibitor.</p>

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

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

<p>AA 863 is a 5-lipoxygenase inhibitor, it inhibits the proliferation of human glioma cell lines in dose-dependent.</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>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>CLB-016 is an inhibitor of hypoxia-inducible factor (HIF)-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>Adibendan (Adibendanum) is a selective inhibitor of PDE3 with an IC50 of 2.0 μM.</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>Darodipine (PY-108068) is a dihydropyridine type Ca+2 antagonist.</p>

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

<p>JGB-1-155, serving as a positive allosteric modulator (N-PAMs), effectively enhances the activity of nicotinamide phosphoribosyltransferase (NAMPT) with an EC 50 of 3.29 μM. It mitigates oxidative stress by elevating NAD+ levels in THP-1 human monocytes and reduces TNFα-induced reactive oxygen species (ROS) in HT-22 cells [1].</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>Hemipyocyanine (528-71-2) is the virulence factor of Gram-negative, aerobic rod bacterium Pseudomonas aeruginosa. Hemipyocyanine is an α-Amylase inhibitor.</p>

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

<p>12,15-Epoxy-13-methyl-12,14-eicosadienoic acid, a furan fatty acid first identified in northern pike (E. lucius), exhibits elevated levels in the liver of starving cod.</p>

<p>ICMT-IN-2 (compound 45) serves as an ICMT inhibitor with an IC50 value of 0.168 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>1-Myristoyl-2-palmitoyl-3-butyryl-rac-glycerol, a triacylglycerol with myristic acid (at the sn-1 position), palmitic acid (at the sn-2 position), and butyric acid (at the sn-3 position), has been detected in human breast milk.</p>

<p>ICMT-IN-30 (compound 67) is an ICMT inhibitor with an IC50 value of 0.27 μM [1].</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>RORγt agonist 2 is a potent agonist of RORγt.</p>

<p>SREBP/SCAP-IN-2 (compound 13) acts as a selective inhibitor of SREBP/SCAP [1].</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>"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>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>Autotaxin-IN-4 is an Autotaxin inhibitor. It has the potential to treat idiopathic pulmonary fibrosis.</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>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>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>ICMT-IN-20 (compound 54) serves as an ICMT inhibitor with an IC50 value of 0.682 μM [1].</p>

<p>RXPA 380: C-terminal ACE inhibitor, Ki=3nM; IC50=2.5nM for C-domain ACE mutants.</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>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>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>ICMT-IN-27, also known as compound 64, is an inhibitor of the enzyme ICMT, demonstrating potent activity with an IC50 value of 0.1 µM [1].</p>

<p>Hypogeic acid is isolable from cultures of autotrophic bacteria linked to sulfate accumulation in biofilters [1].</p>

<p>Anandamide (AEA), an endogenous cannabinoid, interacts with both central (CB1) and peripheral (CB2) cannabinoid receptors. Its effects are concluded through the cellular uptake and enzymatic breakdown of its amide bond by fatty acid amide hydrolase. Arachidonoyl-N-methyl amide, an analog of anandamide, specifically targets the human CB1 receptor, displaying a binding affinity with a Ki of 60 nM. It completely inhibits rat glial gap junction intercellular communication at a concentration of 50 µM.</p>

<p>Cis-8-Octadecenoic acid, a monounsaturated fatty acid and isomer of oleic acid, trans-vaccenic acid, trans-petroselinic acid, and cis-petroselinic acid, is present in partially hydrogenated vegetable oil and milk fat.</p>

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

<p>G1-OC2-K3-E10, an ionizable lipid, facilitates mRNA delivery through lipid nanoparticles (LNPs) [1].</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>(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>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>MAGL-IN-6, a powerful MAGL blocker, IC50 at 4.71 nM, may assist in neurological disease research.</p>

<p>QH536 degrades HMGCR (EC50: 0.22 μM), has anti-inflammatory properties, and avoids cholesterol buildup; useful for cardiovascular and NASH research.</p>

<p>FR-190809 is a nonadrenotoxic and orally efficacious inhibitor of acyl-CoA:cholesterol O-acyltransferase (ACAT) (IC50: 45 nM).</p>

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

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

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

<p>(S,R)-WT IDH1 Inhibitor 2: selectively targets mutant IDH1; IC50 - R132G: 2.9 nM, R132C: 3.8 nM, R132H: 4.6 nM, WT: 46 nM; potential for AML treatment.</p>

<p>DHODH-IN-22: potent, selective DHODH inhibitor, orally active, IC50: 0.3 nM, for AML research.</p>

<p>LNP Lipid-8 (11-A-M), an ionizable lipid, is utilized in lipid nanoparticles (LNP) for siRNA delivery to T cells without ligand targeting. When loaded with GFP siRNA (siGFP), it significantly silences the GFP gene in a mouse model [1].</p>

<p>SH-BC-893: Oral anti-cancer sphingolipid analog, prevents ceramide-related mitochondrial issues, and tackles diet-related obesity.</p>

<p>FXa-IN-1, an FXa blocker: IC50=3 nM, Ki=0.7 nM, orally available, long half-life, for thrombosis research.</p>

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

<p>(Rac)-Lonafarnib is a racemic FTase inhibitor, effective against H-ras, K-ras, N-ras (IC50: 1.9, 5.2, 2.8 nM), and has anti-HDV properties.</p>

<p>Moexiprilat, an active metabolite of the prodrug moexipril formed through side chain ester hydrolysis in vivo, functions as an angiotensin-converting enzyme (</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>NUCC-0223619 is an IDO1 inhibitor that induces the degradation of IDO protein and can be involved in the synthesis of PROTAC.</p>