FR-167356 is a specific inhibitor of a3 isoform vacuolar type H⁺-ATPase with IC50s of 170 nM, 370 nM and 220 nM for osteoclast plasma membranes, renal brush border membranes and macrophage microsomes. FR-167356 reduces bone metastasis of B16-F10 cells.

Furegrelate sodium (U-63557A) is a selective thromboxane synthase inhibitor with oral activity. Furegrelate sodium(U-63557A) inhibits thromboxane A2 (TXA2) synthase in human platelet microsomes with an IC50 of 15 nM.

Estradiol 3-sulfamate (BLE 00084) is an orally active and highly potent steroidal estrone sulfatase (ES) inhibitor.Estradiol 3-sulfamate has a K(i) value of 73 nM for ES in human placental microsomes and can be used in the study of breast cancer.

(S)-Lisofylline is the inactive optical enantiomer of (R)-lisofylline which is an anti-inflammatory agent. (S)-Lisofylline is exclusively converted to pentoxifylline in human liver microsomes.

6-Hydroxy-TSU-68, a derivative and metabolite of TSU-68, reflects the compound's self-induced hydroxylation in human liver microsomes [1].

S-Benzylglutathione acts as a competitive inhibitor of glutathionase and undergoes conversion by rat kidney microsomes into its cysteine derivatives. It is utilized in studies concerning the metabolic degradation of glutathione via the glutathionase system [1].

(±)8,9-DiHETE is a major metabolite of the 20:5 ω-3 fatty acid eicosapentaenoic acid .[1] It is produced in rat liver microsomes, but not renal microsomes, by the generation of the unstable intermediate 8,9-epoxy eicosatetraenoic acid from EPA by cytochrome P450 monooxygenases. Dietary EPA supplementation in humans results in substantial urinary excretion of vicinal diols, including 8,9, 11,12, and 14,15 forms.[2]

(±)16-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. (±)16-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

Mirtazapine N-oxide is a metabolite of mirtazapine.1It is formed from mirtazapine by the cytochrome P450 (CYP) isoforms CYP1A2 and CYP3A4 in human liver microsomes.

Vonoprazan Fumarate (TAK438) , a novel potassium-competitive acid blocker, inhibits gastric acid secretion. Vonoprazan Fumarate (TAK438) inhibited H+,K+-ATPase activity in porcine gastric microsomes with IC50 value of 19 nM at pH 6.5.

S-(p-Nitrobenzyl)glutathione acts as a competitive inhibitor of glutathionase. Rat kidney microsomes convert this compound into associated cysteine derivatives. It serves as a research tool in investigating the catabolism of glutathione by the glutathionase system [1] [2].

(±)14-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. DHA is metabolized to 14(S)-HDHA by human platelets along with 11(S)-HDHA. 14(S)-HDoHE is also produced by salmon gills upon stimulation with calcium ionophore. 14(S)-HDHA was shown to be an inhibitor of U-46619-induced human platelet aggregation and rabbit and rat aortic smooth muscle contraction with IC50 values of about 70, 3.6, and 5.3 μM, respectively. (±)14-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

N-desmethyl Eletriptan is a metabolite of eletriptan .1It is formed from eletriptan primarily by the cytochrome P450 (CYP) isoform CYP3A4 in human liver microsomes. 1.Evans, D.C., O’Connor, D., Lake, B.G., et al.Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoproteinDrug Metab. Dispos.31(7)861-869(2003)

(±)17-HDHA is an autoxidation product of docosahexaenoic acid in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. 17(S)-HDHA could be produced by enzymatic oxidation of DHA using soybean lipoxygenase (LO) and is the putative product of mammalian 15-LOs. 17(S)-HDHA was shown to be an inhibitor of U-46619 -induced rabbit and rat aortic smooth muscle contraction with IC50 values of 4.9 and 7.2 μM, respectively. (±)17-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

Aflatoxin Q1, a hydroxy metabolite of Aflatoxin B1 (AFB1)—a mycotoxin synthesized by Aspergillus flavus (A. flavus)—and aflatoxin B1 8,9-oxide are principal oxidative derivatives produced from Aflatoxin B1 in human liver microsomes across all substrate concentrations. The conversion of Aflatoxin B1 to Aflatoxin Q1 through 3 alpha-hydroxylation represents a critical detoxification route [1] [2].

Enniatin A, a Fusarium mycotoxin, inhibits acyl-CoA: cholesterol acyltransferase (ACAT) with an IC50 of 22 μM in rat liver microsome enzyme assays.

C2 Adamantanyl Galactosylceramide (d18:1/2:0) (AdaGalCer) is a bioactive sphingolipid. It reduces globotriaosylceramide 3 synthesis from exogenous lactosylceramide in microsomes. AdaGalCer stimulates recombinant glucocerebrosidase activity in a pH-dependent manner. It activates glucocerebrosidase to decrease glucosylceramide accumulation in fibroblasts and lymphoblasts isolated from patients with Gaucher and Fabry disease, respectively.

(±)11-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. DHA is metabolized to 11(S)-HDHA by human platelets and canine retina. In addition to 11(S)-HDHA, 14(S)-HDHA is also produced by platelets. 11(S)-HDHA was shown to be an inhibitor of U-46619-induced human platelet aggregation and rabbit and rat aortic smooth muscle contraction with IC50 values of about 50, 4.7, and 7.5 μM, respectively. (±)11-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

Thielavin A is a fungal metabolite originally isolated from T. terricola that is related to thielavin B . Thielavin A inhibits COX, blocking both the conversion of arachidonic acid to prostaglandin H2 and the conversion of PGH2 to PGE2 . Thielavin A also inhibits glucose-6-phosphatase in rat liver microsomes (IC50 = 4.6 μM). It is a non-competitive inhibitor of α-glucosidase from S. cerevisiae (IC50 = 23.8 μM; Ki = 27.8 μM).

(±)13-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. Fresh water hydra was shown to metabolize DHA to 13(R)-HDHA, presumably via the 11R-lipoxygenase activity. (±)13-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

(±)10-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro.[1][2] It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes.[3][4][5] (±)10-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid. Reference：[1]. VanRollins, M., and Murphy, R.C. Autooxidation of docosahexaenoic acid: Analysis of ten isomers of hydroxydocosahexaenoate. J. Lipid Res. 25(5), 507-517 (1984).[2]. Reynaud, D., Thickitt, C.P., and Pace-Asciak, C.R. Facile preparation and structural determination of monohydroxy derivatives of docosahexaenoic acid (HDoHE) by α-tocopherol-directed autoxidation. Anal. Biochem. 214(1), 165-170 (1993).[3]. VanRollins, M., Baker, R.C., Sprecher, H., et al. Oxidation of docosahexaenoic acid by rat liver microsomes. J. Biol. Chem. 259(9), 5776-5783 (1984).[4]. Yamane, M., Abe, A., and Yamane, S. High-performance liquid chromatography-thermospray mass spectrometry of epoxy polyunsaturated fatty acids and epoxyhydroxy polyunsaturated fatty acids from an incubation mixture of rat tissue homogenate. J. Chromatogr. 652(2), 123-136 (1994).[5]. Kim, H.Y., Karanian, J.W., Shingu, T., et al. Sterochemical analysis of hydroxylated docosahexaenoates produced by human platelets and rat brain homogenate. Prostaglandins 40(5), 473-490 (1990).

6-hydroxy Chlorzoxazone is a metabolite of chlorzoxazone. [1] It is formed by metabolism of chlorzoxazone by the cytochrome P450 (CYP) isoform CYP2E1 in human hepatic microsomes.

7-Hydroxy-TSU-68 is a derivative and metabolite of TSU-68, originating from the self-induced hydroxylation of TSU-68 in human liver microsomes, indicative of its biotransformation pathway [1].

(±)7-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. Enzymatic transformation of DHA by RBL-1 cells and human neutrophils also produces 7-HDHA. However, the enzymatic product is most likely the S-isomer. (±)7-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

Sorafenib N-oxide is an active metabolite of sorafenib , an inhibitor of Raf-1, B-RAF, and receptor tyrosine kinases. Sorafenib N-oxide inhibits FLT3 that contains the internal tandem duplication mutation (FLT3-ITD; Kd = 70 nM) and inhibits proliferation of MV4-11 acute myeloid leukemia (AML) cells expressing FLT3-ITD (IC50 = 25.8 nM). It is selective for AML cell lines containing FLT3-ITD over lines containing wild-type FLT3 (IC50s = 3.9-13.3 μM). Sorafenib N-oxide is also a linear-mixed inhibitor of the cytochrome P450 (CYP) isoform CYP3A4 (Ki = 15 μM in human liver microsomes).

N-hydroxy Riluzole is a metabolite of the antiglutamatergic agent riluzole .1It is formed from riluzole predominantly by the cytochrome P450 (CYP) isoform CYP1A2 in human hepatic microsomes. 1.Sanderink, G.J., Bournique, B., Stevens, J., et al.Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitroJ. Pharmacol. Exp. Ther.282(3)1465-1472(1997)

Enniatins B decreases the activation of ERK (p44/p42). Enniatin B is a Fusarium mycotoxin. Enniatin B inhibits acyl-CoA: cholesterol acyltransferase (ACAT) activity with an IC50 of 113 μM in an enzyme assay using rat liver microsomes.

Enniatin B1, a Fusarium mycotoxin, crosses the blood-brain barrier, decreases the activation of ERK (p44/p42), and inhibits moderately TNF-α-induced NF-κB activation. Furthermore, it inhibits acyl-CoA: cholesterol acyltransferase (ACAT) activity, exhibiting an IC50 of 73 μM in rat liver microsome enzyme assays.

16α-hydroxy Dehydroepiandrosterone is a metabolite of the endogenous steroid hormone dehydroepiandrosterone .116α-hydroxy Dehydroepiandrosterone is formed from dehydroepiandrosteronevia16-hydroxylation by the cytochrome P450 (CYP) isoforms CYP3A4 and CYP3A5 in adult human liver microsomes, as well as by fetal recombinant CYP3A7. It is a precursor to fetal estrogens, including estriol .2 1.Miller, K.K.M., Cai, J., Ripp, S.L., et al.Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone (DHEA) metabolites produced by liver microsomal cytochromes P450Drug. Metab. Dispos.32(3)305-313(2004) 2.Hampl, R., and Starka, L.Minireview: 16α-Hydroxylated metabolites of dehydroepiandrosterone and their biological significanceEndocr. Regul.34(3)161-163(2000)

Methyl diethyldithiocarbamate is an active metabolite of the aldehyde dehydrogenase inhibitor disulfiram .1It is produced by methylation of the disulfiram metabolite diethyldithiocarbamate in mouse liver microsomes.2Methyl diethyldithiocarbamate inhibits liver low Kmaldehyde dehydrogenase (ALDH) in rats (ID50= 15.5 mg/kg).1It decreases mean arterial pressure (MAP) and increases heart rate during ethanol challenge in rats when administered at a dose of 20.6 mg/kg. 1.Hart, B.W., Yourick, J.J., and Faiman, M.D.S-methyl-N,N-diethylthiolcarbamate: A disulfiram metabolite and potent rat liver mitochondrial low Km aldehyde dehydrogenase inhibitorAlcohol7(2)165-169(1990) 2.Gessner, T., and Jakubowski, M.Diethyldithiocarbamic acid methyl ester. A metabolite of disulfiramBiochem. Pharmacol.21(2)219-230(1972)

(±)4-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. Enzymatic transformation of DHA by RBL-1 cells also produces 4-HDHA. However, the enzymatic product is most likely the S-isomer. (±)4-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

5-hydroxy Indomethacin is a metabolite of indomethacin .1It is formed from indomethacin in rabbit hepatic microsomes. 1.Evans, M.A., Papazafiratou, C., Bhat, R., et al.Indomethacin metabolism in isolated neonatal and fetal rabbit hepatocytesPediatr. Res.15(11)1406-1410(1981)

Enniatin A1, a cyclic hexadepsipeptide composed of alternating D-α-hydroxyisovaleric acids and N-methyl-L-amino acids isolated from Fusarium mycotoxins, exhibits anticarcinogenic effects through the induction of apoptosis and disruption of the ERK signaling pathway. It also inhibits ACAT in rat liver microsomes with an IC50 of 49 μM.

S6K2-IN-1 (Compound 2) is an inhibitor of S6K2 with an IC50 of 22 nM and also exhibits inhibitory activity against FGFR4 with an IC50 of 216 nM. This compound demonstrates acceptable stability in mouse liver microsomes [1].

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.

Citreoviridin, a toxin from Penicillium citreoviride NRRL 2579, inhibits brain synaptosomal Na+/K+-ATPase whereas, in microsomes, both Na+/K+-ATPase and Mg2+-ATPase activities are significantly stimulated in a dose-dependent manner.

AMK is an active metabolite of the neurohormone melatonin .1,2,3,4It is formed from melatoninviathe metabolic intermediate AFMK that is then deformylated by catalase or formamidase.5,6AMK scavenges singlet oxygenin vitrowhen used at a concentration of 200 μM.1It inhibits the epinephrine- and arachidonic acid-induced production of prostaglandin E2and PGD2in ovine seminal vesicle microsomes in a concentration- and time-dependent manner, as well as LPS-induced increases in COX-2 levels in RAW 264.7 macrophages when used at a concentration of 500 μM.2,3AMK (20 mg/kg) decreases MPTP-induced increases in lipid peroxidation in the cytosol and mitochondria from substantia nigra and striatum in a mouse model of MPTP-induced Parkinson’s disease.4 1.Schaefer, M., and Hardeland, R.The melatonin metabolite N1-acetyl-5-methoxykynuramine is a potent singlet oxygen scavengerJ. Pineal Res.46(1)49-52(2009) 2.Kelly, R.W., Amato, F., and Seamark, R.F.N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesisBiochem. Biophys. Res. Commun.121(1)372-379(1984) 3.Mayo, J.C., Sainz, R.M., Tan, D.-X., et al.Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophagesJ. Neuroimmunol.165(1-2)139-149(2005) 4.Tapias, V., Escames, G., López, L.C., et al.Melatonin and its brain metabolite N1-acetyl-5-methoxykynuramine prevent mitochondrial nitric oxide synthase induction in parkinsonian miceJ. Neurosci. Res.87(13)3002-3010(2009) 5.Tan, D.-X., Manchester, L.C., Reiter, R.J., et al.Melatonin directly scavenges hydrogen peroxide: A potentially new metabolic pathway of melatonin biotransformationFree Radic. Biol. Med.29(11)1177-1185(2000) 6.Hirata, F., Hayaishi, O., Tokuyama, T., et al.In vitro and in vivo formation of two new metabolites of melatoninJ. Biol. Chem.249(4)1311-1313(1974)

(±)8-HDHA is an autoxidation product of docosahexaenoic acid (DHA) in vitro. It is also produced from incubations of DHA in rat liver, brain, and intestinal microsomes. (±)8-HDHA is a potential marker of oxidative stress in brain and retina where DHA is an abundant polyunsaturated fatty acid.

1a,1b-dihomo Prostaglandin E2 (PGE2) is a rare polyunsaturated fatty acid first identified in extracts of sheep vesicular gland microsomes, known to contain COX, incubated with adrenic acid . 1a,1b-dihomo PGE2 has also been identified in conditioned media of RAW 264.7 macrophages stimulated with endotoxin and arachidonic acid . This product is thought to be produced by elongation of AA to adrenic acid, which is then metabolized sequentially by COX and PGE synthase.

20-carboxy Arachidonic acid (20-COOH-AA) is the major metabolite of 20-HETE that is produced in renal tubular epithelial, endothelial, and microvascular smooth muscle cell cultures. This ω-oxidation conversion can take place using purified alcohol dehydrogenases three and four or by microsomes containing recombinant human CYP4F3B. Like 20-HETE, 20-COOH-AA inhibits ion transport in the kidneys. It also produces vasorelaxation of porcine coronary microvessels constricted with endothelin. 20-COOH-AA binds to isolated ligand binding domains of peroxisome proliferator-activated receptor α (PPARα) (Kd = 0.87 ± 0.12 μM) and PPARγ (Kd = 1.7 ± 0.5 μM), and is a dual activator of PPARα and PPARγ in a transiently transfected COS-7 cell reporter system.

(+)-Cevimeline hydrochloride hemihydrate ((+)-SNI-2011), a potent muscarinic receptor agonist, stands as a promising therapeutic candidate for treating xerostomia in Sjogren's syndrome. This compound has demonstrated a broad pharmacological profile across various systems including gastrointestinal, urinary, and reproductive, in animal models such as mice, rats, guinea pigs, rabbits, and dogs. Its metabolism was assessed in vitro using rat and dog liver microsomes, revealing that (+)-SNI-2011 is rapidly absorbed with peak plasma concentrations (Cmax) reached within one hour post-oral administration, followed by a decline with a half-life (t1/2) ranging from 0.4 to 1.1 hours. Bioavailability was recorded at 50% in rats and 30% in dogs. Metabolic analysis indicated species-specific differences, with rats producing both S- and N-oxidized metabolites and dogs only producing N-oxidized metabolites. Additionally, sex-based differences in pharmacokinetics were observed in rats but not in dogs. The in vitro study highlighted the involvement of cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in the sulfoxidation and N-oxidation of SNI-2011, respectively, with CYP2D and CYP3A being primarily responsible for sulfoxidation in rat liver microsomes.

LY 43578 is an orally active aromatase inhibitor. LY43578 could inhibit O-demethylation of P-450-dependent p-nitroanisole and N-demethylation of ethylmorphine (IC50 of 0.3 and 5 μm, respectively) in rat liver microsomes. LY 43578 can be used to study neurological and cardiovascular diseases.

Mal-PEG4-VC-PAB-DMEA-PNU-159682 is a drug-linker conjugate designed for antibody-drug conjugate (ADC) therapy. It combines the ADC linker, Mal-PEG4-VC-PAB, with the potent ADC cytotoxin, DMEA-PNU-159682. The cytotoxin, DMEA-PNU-159682, is derived from metabolites of nemorubicin (MMDX) found in liver microsomes, as well as the ADC cytotoxin PNU-159682[1].

Vinclozolin M2, an active metabolite of vinclozolin, is generated through successive esterase activity and decarboxylation in C. elegans, as well as decarboxylation in human liver microsomes. It functions as an antagonist to the mineralocorticoid (IC50= 1,400 nM) and androgen receptors (IC50= 0.17 nM), demonstrated in reporter assays with MCF-7 cells. This compound is exclusively sold for research and analytical purposes, tailored for controlled laboratory use, and is not available in bulk sizes.

7beta-(3-Ethyl-cis-crotonoyloxy)-1alpha-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone shows diacylglycerol acyltransferase (DGAT)1 inhibition with IC(50) values of 47.0 microM (for rat liver microsomes) and 160.7 microM (for HepG2 cell microsomes),

hCYP3A4-IN-1 (compound C6) is a potent, orally active inhibitor of hCYP3A4, exhibiting IC50 values of 43.93 nM in human liver microsomes (HLMs) and 153.00 nM in the CHO-3A4 stably transfected cell line. It competitively inhibits the CYP3A4-mediated hydroxylation of N-ethyl-1,8-naphthalimide (NEN) with a Ki of 30.00 nM [1].

PRMT5-IN-31 (Compound 3m), a selective PRMT5 inhibitor (IC50: 0.31 μM), increases hnRNP E1 protein levels by occupying the substrate site of PRMT5 and establishing key interactions with amino acid residues. It exhibits antiproliferative properties against A549 cells through induction of apoptosis and inhibition of cell migration, while demonstrating high metabolic stability in human liver microsomes (T1/2: 132.4 min) [1].

LU 49888 is a photoaffinity analog of verapamil that has been used to identify specific binding sites for phenylalkylamines of calcium channels present in rabbit skeletal muscle microsomes.

(R)-Omeprazole is the inactive isomer of omeprazole , a gastric proton-pump inhibitor. A stereoselective hydroxylation of (R)-omeprazole is mediated primarily by cytochrome P450 (CYP) 2C19, whereas CYP3A4 favors sulfoxidation of the active (S)-enantiomer . (R)-Omeprazole has been shown to act as a reversible direct-acting and metabolism-dependent inhibitor of CYP2C19 in pooled human liver microsomes (IC50 = 8.1 μM).

22-HDHA is an oxidation product of docosahexaenoic acid . In vitro, it is formed upon incubation of rat liver microsomes with DHA and NADPH and also by the human cytochrome P450 (CYP) isoform CYP4F3B in BTI-TN-5B1-4 microsomes. Serum levels of 22-HDHA increase following dietary DHA supplementation in humans.