Erlotinib-13C6 (CP-358774-13C6) is a 13C-labeled Erlotinib. Erlotinib is a directly acting EGFR tyrosine kinase inhibitor, with an IC50 of 2 nM for human EGFR[1]. Erlotinib reduces EGFR autophosphorylation in intact tumor cells with an IC50 of 20 nM. Erlotinib is used for the treatment of non-small cell lung cancer[1].Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process[2]. [1]. Moyer JD, et al. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. 1997, 57(21), 4838-4848.[2]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216.
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)
5-Fluorouracil-13C,15N2 is intended for use as an internal standard for the quantification of 5-flurouracil by GC- or LC-MS. 5-Fluorouracil is a pyrimidine analog that irreversibly inhibits thymidylate synthase, blocking the synthesis of thymidine which is required for DNA synthesis. Intracellular metabolites of 5-fluorouracil exert cytotoxic effects by either inhibiting thymidylate synthetase, or through incorporation into RNA and DNA, ultimately initiating apoptosis.
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).
1,2,3-Trioctanoyl-rac-glycerol-13C3 is intended for use as an internal standard for the quantification of 1,2,3-trioctanoyl-rac-glycerol by GC- or LC-MS. 1,2,3-Trioctanoyl-rac-glycerol is a triacylglycerol that contains octanoic acid at the sn-1, sn-2, and sn-3 positions. Dietary administration of 1,2,3-trioctanoyl-rac-glycerol increases hippocampal levels of the glycolytic metabolites glucose 6-phosphate, fructose 6-phosphate, and β-hydroxybutyrate and the seizure threshold in the 6 Hz psychomotor seizure test in mice.1 Formulations containing 1,2,3-trioctanoyl-rac-glycerol have been used in cosmetic products as thickening and skin-conditioning agents.
Nitisinone-13C6is intended for use as an internal standard for the quantification of nitisinone by GC- or LC-MS. Nitisinone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), which converts 4-hydroxyphenylpyruvate (HPPA) to homogentisate in the tyrosine catabolic pathway.1Nitisinone increases urinary levels of HPPA and 4-hydroxyphenyllactate (HPLA) in rats when administered at a dose of 10 mg kg. Nitisinone (3 mg kg) prevents the neonatal lethality of fumarylacetoacetate hydrolase (FAH) deficiency in mice when administered to pregnant dams.2It exhibits hepatoprotective effects inFAH- -mice, such as prevention of increases in plasma levels of aspartate serine aminotransferase (AST) and conjugated bilirubin, when administration is continued following birth at a dose of 1 mg kg. Nitisinone (100 μg) decreases urinary excretion of homogentisate and increases urinary excretion of HPPA, HPLA, and 4-hydroxyphenylacetate in a mouse model of alkaptonuria induced by ethylnitrosourea.3Formulations containing nitisinone have been used in the treatment of hereditary tyrosinemia type 1 (HT-1). 1.Ellis, M.K., Whitfield, A.C., Gowans, L.A., et al.Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dioneToxicol. Appl. Pharmacol.133(1)12-19(1995) 2.Grompe, M., Lindstedt, S., al-Dhalimy, M., et al.Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type INat. Genet.10(4)453-460(1995) 3.Suzuki, Y., Oda, K., Yoshikawa, Y., et al.A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuriaJ. Hum. Genet.44(2)79-84(1999)
Cefazolin-13C2,15N is intended for use as an internal standard for the quantification of cefazolin by GC- or LC-MS. Cefazolin is a broad-spectrum cephalosporin antibiotic that is active in vitro against various Gram-positive and Gram-negative bacteria (MICs = 0.2-12.5 μg ml). It also inhibits the growth of clinical isolates of S. aureus, E. coli, P. mirabilis, and K. pneumoniae (MICs = 0.1-25 μg ml). In vivo, cefazolin protects against S. aureus, E. coli, and P. mirabilis infection in mice (ED50s = <0.09-1.78, 0.44-3.63, and 2.31-5.2 mg animal, respectively). Formulations containing cefazolin have been used to treat a variety of bacterial infections.
1,2-Dioleoyl-rac-glycerol-13C3 is intended for use as an internal standard for the quantification of 1,2-dioleoyl-rac-glycerol by GC- or LC-MS. 1,2-dioleoyl-rac-glycerol is a diacylglycerol that contains oleic acid at the sn-1 and sn-2 positions. It effectively binds the C1 domain to activate conventional protein kinase C forms and serves as a substrate for diacylglycerol kinases and multisubstrate lipid kinase.1,2,3 |1. Yamaguchi, Y., Shirai, Y., Matsubara, T., et al. Phosphorylation and up-regulation of diacylglycerol kinase γ via its interaction with protein kinase Cγ. J. Biol. Chem. 281(42), 31627-31637 (2006).|2. Zhou, Q.Z., Raynor, R.L., Wood, M.G., Jr., et al. Structure-activity relationship of synthetic branched-chain distearoylglycerol (distearin) as protein kinase C activators. Biochemistry 27(19), 7361-7365 (1988).|3. Epand, R.M., Shulga, Y.V., Timmons, H.C., et al. Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. Biochemistry 46(49), 14225-14231 (2007).
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
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 |1. Dippold, M.A., and Kuzyakov, Y. Direct incorporation of fatty acids into microbial phospholipids in soils: Position-specific labeling tells the story. Geochim. Cosmochim. Acta 174(1), 211-221 (2016).|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 patients. Ann. Nutr. Metab. 39(1), 52-62 (1995).|3. 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).|4. 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).|5. 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).|6. 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).|7. 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).
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)
13C C16 Sphingomyelin is an isotopically enriched form of C16 sphingomyelin with carbon-13 occurring on the fatty acid portion. It is intended for use as an internal standard for the quantification of C16 sphingomyelin by GC- or LC-MS. C16 Sphingomyelin is a form of sphingomyelin containing palmitate (16:0) at the variable acylation position. It is the most common form of sphingomyelin found in eggs and is less abundant in the brain and in milk. C16 Sphingomyelin interacts with cholesterol in ordered lipid domains (lipid rafts). Sphingomyelinases remove phosphorylcholine from C16 sphingomyelin to produce C16 ceramide. While ceramides commonly induce apoptosis, ceramides with different fatty acid chain lengths might direct distinct functions and, in some cases, reduce apoptosis.
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)
Lamivudine 13C,15N2, an impurity of Lamivudine (BCH-189), functions as an inhibitor of both HIV-1/2 reverse transcriptase and hepatitis B virus reverse transcriptase, classifying it as a nucleoside reverse transcriptase inhibitor (NRTIs).
Caffeic acid-13C3 is an isotopically enriched form of caffeic acid that is intended for use as an internal standard for the quantification of caffeic acid by GC- or LC-MS. Caffeic acid is an inhibitor of 5-LO , with IC50 values of 3.7-72 μM, and 12-LO, with IC50 values of 5.1-30 μM.
Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg kg, respectively). Zonisamide (40 mg kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).