lc-ms

MAK683 是胚胎外胚层发育 (EED) 抑制剂。在 EED Alphascreen 结合、LC-MS 和 ELISA 测定中，IC50值为 59、89 和 26 nM。

MAK683 hydrochloride胚胎外胚层发育 (EED) 抑制剂，也是一种高效的 PRC2 抑制剂，可阻断癌细胞增殖（IC50=1.014），在EED Alphascreen， ELISA 和 LC-MS 试验中测得的IC50 值分别为 59，26，89 nM。

TAK632 是一种有效的pan-RAF 抑制剂，对CRAF、BRAFV600E 和BRAFWT 的IC50分别为 1.4、2.4 和 8.3 nM。

13C15-Nivalenol is intended for use as an internal standard for the quantification of nivalenol by GC- or LC-MS. Nivalenol is a trichothecene mycotoxin that has been found inFusarium.1It is lethal to mice (LD50= 6.9 mg kg).2Nivalenol (5, 10, and 15 mg kg) also induces thymic, splenic, and Peyer's patch cell apoptosis in mice.3 1.Yang, Z., Concannon, J., Ng, K.S., et al.Tetrandrine identified in a small molecule screen to activate mesenchymal stem cells for enhanced immunomodulationSci. Rep.630263(2016) 2.Yoshizawa, T., and Morooka, N.Studies on the toxic substances in the infected cereals (part 3): Acute toxicities of new trichothecene mycotoxins: Deoxynivalenol and its monoacetateJ. Food Hyg.15(4)261-269(1974) 3.Poapolathep, A., Ohtsuka, R., Kiatipattanasakul, W., et al.Nivalenol-induced apoptosis in thymus, spleen and Peyer's patches of miceExp. Toxicol. Pathol.53(6)441-446(2002)

3-Acetyldeoxy nivalenol-13C17is intended for use as an internal standard for the quantification of 3-acetyldeoxy nivalenol by GC- or LC-MS. 3-Acetyldeoxy nivalenol is a mycotoxin that has been found inF. graminearum.1In vivo, 3-acetyldeoxy nivalenol (40 mg kg) induces duodenal and splenic cell necrosis, as well as lethality (LD50= 70 mg kg) in mice.2 1.Jiao, F., Kawakami, A., and Nakajima, T.Effects of different carbon sources on trichothecene production and Tri gene expression by Fusarium graminearum in liquid cultureFEMS Microbiol.Lett.285(2)212-219(2008) 2.Schiefer, H.B., Nicholson, S., Kasali, O.B., et al.Pathology of acute 3-acetyldeoxynivalenol toxicity in miceCan. J. Comp. Med.49(3)315-318(1985)

4-deoxy Nivalenol-13C15is intended for use as an internal standard for the quantification of 4-deoxy nivalenol by GC- or LC-MS. 4-deoxy Nivalenol is a trichothecene mycotoxin that has been found inFusarium.1It binds to eukaryotic ribosomes and inhibits protein synthesis in mice when administered at doses ranging from 5 to 25 mg kg. 4-deoxy Nivalenol (0.1 and 0.2 mg kg) induces emesis in pigs and decreases feed consumption in pigs when administered at a dose of 40 ppb in the diet.2It induces lethality in mice (LD50= 46-78 mg kg).34-deoxy Nivalenol has been found inF. graminearum-infected cereal grains such as wheat, barley, and corn. 1.Pestka, J.J., and Smolinski, A.T.Deoxynivalenol: Toxicology and potential effects on humansJ.Toxicol.Environ.Health B.Crit.Rev.8(1)39-69(2005) 2.Forsyth, D.M., Yoshizawa, T., Morooka, N., et al.Emetic and refusal activity of deoxynivalenol to swineAppl. Environ. Microbiol.34(5)547-552(1977) 3.Pestka, J.J.Deoxynivalenol: Mechanisms of action, human exposure, and toxicological relevanceArch. Toxicol.84(9)663-679(2010)

Aflatoxin B2-13C17(AFB2-13C17) is intended for use as an internal standard for the quantification of AFB2by GC- or LC-MS. AFB2is a mycotoxin that has been found inA. terricola.1It induces hepatic autophagy and apoptosis in broiler chickens when administered at doses of 0.2, 0.4, and 0.8 mg kg.2AFB2(0.5 and 1 mg animal) also induces parenchymal cell hyperplasia in rats.3 1.Moubasher, A.H., el-Kady, I.A., and Shoriet, A.Toxigenic Aspergilli isolated from different sources in EgyptAnn. Nutr. Aliment.31(4-6)607-615(1977) 2.Chen, B., Li, D., Li, M., et al.Induction of mitochondria-mediated apoptosis and PI3K Akt mTOR-mediated autophagy by aflatoxin B2 in hepatocytes of broilersOncotarget7(51)84989-84998(2016) 3.Wogan, G.N., Edwards, G.S., and Newberne, P.M.Structure-activity relationships in toxicity and carcinogenicity of aflatoxins and analogsCancer Res.31(12)1936-1942(1971)

Aflatoxin G1-13C17is intended for use as an internal standard for the quantification of aflatoxin G1by GC- or LC-MS. Aflatoxin G1is a mycotoxin that has been found inA. terricola.1In vivo, aflatoxin G1is lethal to ducklings (LD50= 1.18 mg kg).2It induces hepatocellular carcinoma tumor formation and lethality in rats when administered at doses of 1.4 and 3 mg animal, respectively. Aflatoxin G1also inhibits liver and kidney succinate dehydrogenase and fumarase, as well as kidney cytochrome oxidase, NADH oxidase, α-glycerophosphate dehydrogenase, isocitrate dehydrogenase, and malate dehydrogenase in rats.3 1.Moubasher, A.H., el-Kady, I.A., and Shoriet, A.Toxigenic Aspergilli isolated from different sources in EgyptAnn. Nutr. Aliment.31(4-6)607-615(1977) 2.Wogan, G.N., Edwards, G.S., and Newberne, P.M.Structure-activity relationships in toxicity and carcinogenicity of aflatoxins and analogsCancer Res.31(12)1936-1942(1971) 3.Bai, N.J., Pai, M.R., and Venkitasubramanian, T.A.Mitochondrial function in aflatoxin toxicityIndian J. Biochem. Biophys.14(4)347-349(1977)

Aflatoxin G2-13C17is intended for use as an internal standard for the quantification of aflatoxin G2by GC- or LC-MS. Aflatoxin G2is a mycotoxin that has been found inAspergillus.1It is lethal to ducklings (LD50= 2.83 mg kg) but is non-toxic to rats when administered at a dose of 200 mg kg.2 1.Bennett, J.W., and Klich, M.MycotoxinsClin. Microbiol. Rev.16(3)497-516(2003) 2.Wogan, G.N., Edwards, G.S., and Newberne, P.M.Structure-activity relationships in toxicity and carcinogenicity of aflatoxins and analogsCancer Res.31(12)1936-1942(1971)

Guanfacine-13C,15N3is intended for us as an internal standard for the quantification of guanfacine by GC- or LC-MS. Guanfacine is an α2-adrenergic receptor (α2-AR) agonist with Kivalues of 93, 1,380, and 3,890 nM for α2A-, α2B-, and α2C-ARs, respectively, in a radioligand binding assay.1It has EC50values of 52, 288, and 602 nM for α2A-, α2B-, and α2C-ARs, respectively, for stimulated [35S]GTPγS binding. It also binds to imidazoline receptor 1 (Ki= 19 nM in a radioligand binding assay).2Guanfacine (0.3-5 mg kg) binds to adrenergic receptors in the central nervous system and lowers blood pressure in hypertensive rats in a dose-dependent manner.3It also improves spatial working memory deficits induced by hypobaric hypoxia in rats.4Formulations containing guanfacine are used in the treatment of high blood pressure and attention deficit hyperactivity disorder (ADHD). 1.Jasper, J.R., Lesnick, J.D., Chang, L.K., et al.Ligand efficacy and potency at recombinant α2 adrenergic receptors: Agonist-mediated [35S]GTPγS bindingBiochem. Pharmacol.55(7)1035-1043(1998) 2.Nikolic, K., Filipic, S., and Agbaba, D.QSAR study of imidazoline antihypertensive drugsBioorg. Med. Chem.16(15)7134-7140(2008) 3.Scholtysik, G.Pharmacology of guanfacineBr. J. Clin. Pharmacol.10(Suppl 1)21S-24S(1980) 4.Kauser, H., Sahu, S., Kumar, S., et al.Guanfacine is an effective countermeasure for hypobaric hypoxia-induced cognitive declineNeuroscience254110-119(2013)

O-Des[2-aminoethyl]-O-carboxymethyl dehydroamlodipine is a major metabolite of the calcium channel inhibitor amlodipine .1 1.Taguchi, R., Naito, T., Sato, H., et al.Validated LC-MS/MS method for the simultaneous determination of amlodipine and its major metabolites in human plasma of hypertensive patientsTher. Drug Monit.39(6)625-631(2017)

D-Fructose-13C6 可用作通过 GC-或 LC-MS 定量 D-果糖的内标。

2-deoxy-D-Glucose-13C6is intended for use as an internal standard for the quantification of 2-deoxy-D-glucose by GC- or LC-MS. 2-deoxy-D-Glucose is a glucose antimetabolite and an inhibitor of glycolysis.1,2It inhibits hexokinase, the enzyme that converts glucose to glucose-6-phosphate, as well as phosphoglucose isomerase, the enzyme that converts glucose-6-phosphate to fructose-6-phosphate.32-deoxy-D-Glucose (16 mM) induces apoptosis in SK-BR-3 cells, as well as inhibits the growth of 143B osteosarcoma cells cultured under hypoxic conditions when used at a concentration of 2 mg ml.4,5In vivo, 2-deoxy-D-glucose (500 mg kg) reduces tumor growth in 143B osteosarcoma and MV522 non-small cell lung cancer mouse xenograft models when used alone or in combination with doxorubicin or paclitaxel .6 1.Kang, H.T., and Hwang, E.S.2-Deoxyglucose: An anticancer and antiviral therapeutic, but not any more a low glucose mimeticLife Sci.78(12)1392-1399(2006) 2.Aft, R.L., Zhang, F.W., and Gius, D.Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: Mechanism of cell deathBr. J. Cancer87(7)805-812(2002) 3.Ralser, M., Wamelink, M.M., Struys, E.A., et al.A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growthProc. Natl. Acad. Sci. USA105(46)17807-17811(2008) 4.Liu, H., Savaraj, N., Priebe, W., et al.Hypoxia increases tumor cell sensitivity to glycolytic inhibitors: A strategy for solid tumor therapy (Model C)Biochem. Pharmacol.64(12)1745-1751(2002) 5.Zhang, X.D., Deslandes, E., Villedieu, M., et al.Effect of 2-deoxy-D-glucose on various malignant cell lines in vitroAnticancer Res.26(5A)3561-3566(2006) 6.Maschek, G., Savaraj, N., Priebe, W., et al.2-deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivoCancer Res.64(1)31-34(2004)

Oleic acid-13C is intended for use as an internal standard for the quantification of oleic acid by GC- or LC-MS. Oleic acid is a monounsaturated fatty acid and a major component of membrane phospholipids that has been found in human plasma, cell membranes, and adipose tissue.1,2 It contributes approximately 17% of the total fatty acids esterified to phosphatidylcholine, the major phospholipid class in porcine platelets.1 Oleic acid inhibits collagen-stimulated platelet aggregation by approximately 90% when used at a concentration of 10 μg ml. It also inhibits fMLF-induced neutrophil aggregation and degranulation by 55 and 68%, respectively, when used at a concentration of 5 μM, similar to arachidonic acid .3 Oleic acid (60 μM) induces release of intracellular calcium in human platelets.4

Lauric acid-13C is intended for use as an internal standard for the quantification of lauric acid by GC- or LC-MS. Lauric acid is a medium-chain saturated fatty acid. It has been found at high levels in coconut oil.1Lauric acid induces the activation of NF-κB and the expression of COX-2, inducible nitric oxide synthase (iNOS), and IL-1α in RAW 264.7 cells when used at a concentration of 25 μM.2

Octanoic acid-13C is intended for use as an internal standard for the quantification of octanoic acid by GC- or LC-MS. Octanoic acid is a medium-chain saturated fatty acid. It has been found in Teleme cheeses made from goat, ovine, or bovine milk.1 Octanoic acid is active against the bacteria S. mutans, S. gordonii, F. nucleatum, and P. gingivalis (IC80s = <125, <125, 1,403, and 2,294 μM, respectively).2 Levels of octanoic acid are increased in the plasma of patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, an inborn error of fatty acid metabolism characterized by hypoketotic hypoglycemia, medium-chain dicarboxylic aciduria, and intolerance to fasting.3,4 |1. Mallatou, H., Pappa, E., and Massouras, T. Changes in free fatty acids during ripening of Teleme cheese made with ewes', goats', cows' or a mixture of ewes' and goats' milk. Int. Dairy J. 13(1-3), 211-219 (2003).|2. Hyang, C.B., Alimova, Y., Myers, T.M., et al. Short- and medium-chain fatty acids exhibit antimicrobial activity for oral microorganisms. Arch. Oral Biol. 56(7), 650-654 (2011).|3. Onkenhout, W., Venizelos, V., van der Poel, P.F.H., et al. Identification and quantification of intermediates of unsaturated fatty acid metabolism in plasma of patients with fatty acid oxidation disorders. Clin. Chem. 41(10), 1467-1474 (1995).|4. Rinaldo, P., O'Shea, J.J., Coates, P.M., et al. Medium-chain acyl-CoA dehydrogenase deficiency. Diagnosis by stable-isotope dilution measurement of urinary n-hexanoylglycine and 3-phenylpropionylglycine. N. Engl. J. Med. 319(20), 1308-1313 (1988).

N-desmethyl Rosuvastatin is an active metabolite of the HMG-CoA reductase inhibitor rosuvastatin .1,2N-desmethyl Rosuvastatin is formed when rosuvastatin undergoes demethylation, primarily by the cytochrome P450 (CYP) isoform CYP2C9 and to a lesser extent by CYP2C19 and CYP3A4.1 1.Macwan, J.S., Ionita, I.A., and Akhlaghi, F.A simple assay for the simultaneous determination of rosuvastatin acid, rosuvastatin-5S-lactone, and N-desmethyl rosuvastatin in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS)Anal. Bioanal. Chem.402(3)1217-1227(2012) 2.Bai, X., Wang, X.P., He, G.D., et al.Simultaneous determination of rosuvastatin, rosuvastatin-5 S-lactone, and N-desmethyl rosuvastatin in human plasma by UPLC-MS/MS and its application to clinical studyDrug Res. (Stuttg.)68(6)328-334(2018)

Gliotoxin-13C13is intended for use as an internal standard for the quantification of gliotoxin by GC- or LC-MS. Gliotoxin is an immunosuppressive mycotoxin produced by pathogenic strains ofAspergillusand other fungi with diverse biological activities.1,2,3,4,5,6,7,8It inhibits 20S proteasomal chymotrypsin activity (IC50= 10 μM), blocking the degradation of IκBα and preventing the activation of NF-κB.2,3Gliotoxin induces apoptosis in monocytes and dendritic cells and reduces phagocytosis by neutrophils.4,5It suppresses viral infection by Nipah and Hendra virus in HEK293T cells (IC50s = 149 and 579 nM, respectively).6Under reducing conditions, gliotoxin inhibits leukotriene A4hydrolase epoxide hydrolase activity, but not aminopeptidase activity, and leukotriene B4synthesis in neutrophils and monocytes.7

HT-2 toxin-13C22is intended for use as an internal standard for the quantification of HT-2 toxin by GC- or LC-MS. HT-2 toxin is a type A trichothecene mycotoxin and an active, deacetylated metabolite of the trichothecene mycotoxin T-2 toxin .1,2Like T-2 toxin, HT-2 toxin inhibits protein synthesis and cell proliferation in plants.2HT-2 toxin also reduces viability of HepG2, A549, HEp-2, Caco-2, A-204, U937, Jurkat, and RPMI-8226 cancer cells with IC50values ranging from 3.1 to 23 ng ml and human umbilical vein endothelial cells with an IC50value of 56.4 ng ml.1It induces oxidative stress, DNA damage, and autophagy in, as well as halts the development of, cultured mouse embryos when used at a concentration of 10 nM.3HT-2 toxin has been found in cereal grains and food products.4,5 1.Nielsen, C., Casteel, M., Didier, A., et al.Trichothecene-induced cytotoxicity on human cell linesMycotoxin Res.25(2)77-84(2009) 2.Nathanail, A.V., Varga, E., Meng-Reiterer, J., et al.Metabolism of the fusarium mycotoxins T-2 toxin and HT-2 toxin in wheatJ. Agric. Food Chem.63(35)7862-7872(2015) 3.Zhang, L., Li, L., Xu, J., et al.HT-2 toxin exposure induces mitochondria dysfunction and DNA damage during mouse early embryo developmentReprod. Toxicol.85104-109(2019) 4.Langseth, W., and Rundberget, T.The occurrence of HT-2 toxin and other trichothecenes in Norwegian cerealsMycopathologia147(3)157-165(1999) 5.Al-Taher, F., Cappozzo, J., Zweigenbaum, J., et al.Detection and quantitation of mycotoxins in infant cereals in the U.S. market by LC-MS MS using a stable isotope dilution assayFood Control72(Part A)27-35(2017)

Ochratoxin A-13C20is intended for use as an internal standard for the quantification of ochratoxin A by GC- or LC-MS. Ochratoxin A is a mycotoxin that has been found inAspergillusandPenicillium.1It increases lipid peroxide levels and the number of apoptotic cells, as well as reduces superoxide dismutase activity in rat kidney when administered at a dose of 120 μg kg.2Topical application of ochratoxin A (80 μg mouse) induces DNA damage, cell cycle arrest at the G0 G1phase, and apoptosis in mouse skin cells.1It also initiates tumor formation in a two-stage mouse skin tumorigenesis model. Ochratoxin A has been found as a contaminant in a variety of foods.3

Zearalenone-13C18is intended for use as an internal standard for the quantification of zearalenone by GC- or LC-MS. Zearalenone is a mycotoxin that has been found inFusariumand has estrogenic activities.1It binds to human estrogen receptor α (ERα) and ERβ (IC50s = 9 and 5.8 nM, respectively).2Zearalenone induces precocious development of mammary tissues in young female pigs and prepucial enlargement in young male pigs.3Zearalenone (1.5-5 mg kg of diet) induces hyperestrogenism in pigs. It also induces degeneration of meiotic chromatin in oocytes and reduces fertility in pigs when administered at a dose of 200 μg kg.4Zearalenone has been found as a contaminant in wheat, maize, and barley and livestock feeds.3,4

Palmitic acid-13C is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid is a 16-carbon saturated fatty acid. It comprises approximately 25% of human total plasma lipids.1 It increases protein levels of COX-2 in RAW 264.7 cells when used at a concentration of 75 μM.2 Palmitic acid is involved in the acylation of proteins to anchor membrane-bound proteins to the lipid bilayer.2,3,4,5,6 |1. Santos, M.J., López-Jurado, M., Llopis, J., et al. Influence of dietary supplementation with fish oil on plasma fatty acid composition in coronary heart disease patients. Ann. Nutr. Metab. 39(1), 52-62 (1995).|2. Lee, J.Y., Sohn, K.H., Rhee, S.H., et al. Saturated fatty acids, but not unsaturated fatty acids, induced the expression of cyclooxygenase-2 mediated through toll-like receptor 4. J. Biol. Chem. 276(20), 16683-16689 (2001).|3. Dietzen, D.J., Hastings, W.R., and Lublin, D.M. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. J. Biol. Chem. 270(12), 6838-6842 (1995).|4. Robinson, L.J., and Michel, T. Mutagenesis of palmitoylation sites in endothelial nitric oxide synthase identifies a novel motif for dual acylation and subcellular targeting. Proc. Nat. Acad. Sci. USA 92(25), 11776-11780 (1995).|5. Topinka, J.R., and Bredt, D.S. N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 20(1), 125-134 (1998).|6. Miggin, S.M., Lawler, O.A., and Kinsella, B.T. Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation. J. Biol. Chem. 278(9), 6947-6958 (2003).

Palmitic acid-13C (C1, C2, C3, and C4 labeled) is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid is a common 16-carbon saturated fat that represents 10-20% of human dietary fat intake and comprises approximately 25 and 65% of human total plasma lipids and saturated fatty acids, respectively.1,2Acylation of palmitic acid to proteins facilitates anchoring of membrane-bound proteins to the lipid bilayer and trafficking of intracellular proteins, promotes protein-vesicle interactions, and regulates various G protein-coupled receptor functions.1Red blood cell palmitic acid levels are increased in patients with metabolic syndrome compared to patients without metabolic syndrome and are also increased in the plasma of patients with type 2 diabetes compared to individuals without diabetes.3,4 1.Fatima, S., Hu, X., Gong, R.-H., et al.Palmitic acid is an intracellular signaling molecule involved in disease developmentCell. Mol. Life Sci.76(13)2547-2557(2019) 2.Santos, M.J., López-Jurado, M., Llopis, J., et al.Influence of dietary supplementation with fish oil on plasma fatty acid composition in coronary heart disease patientsAnn. Nutr. Metab.39(1)52-62(1995) 3.Yi, L.-Z., He, J., Liang, Y.-Z., et al.Plasma fatty acid metabolic profiling and biomarkers of type 2 diabetes mellitus based on GC/MS and PLS-LDAFEBS Lett.580(30)6837-6845(2006) 4.Kabagambe, E.K., Tsai, M.Y., Hopkins, P.N., et al.Erythrocyte fatty acid composition and the metabolic syndrome: A National Heart, Lung, and Blood Institute GOLDN studyClin. Chem.54(1)154-162(2008)

Palmitic acid-13C is intended for use as an internal standard for the quantification of palmitic acid by GC- or LC-MS. Palmitic acid-13C contains 13C at the C2 position and has been used in the study of free fatty acid incorporation into phospholipid fatty acids in soil microbes.1 Palmitic acid is a 16-carbon saturated fatty acid. It comprises approximately 25% of human total plasma lipids.2 It increases protein levels of COX-2 in RAW 264.7 cells when used at a concentration of 75 μM.3 Palmitic acid is involved in the acylation of proteins to anchor membrane-bound proteins to the lipid bilayer.3,4,5,6,7