(r)-or-s-1

(R)-OR-S1 is a SAM-competitive, highly selective, orally bioavailable dual inhibitor of EZH1/2.

Adenosine 5'-methylenediphosphate is an inhibitor of ecto-5'-nucleotidase, also known as CD73, with a Kivalue of 37 nM.1It inhibits cAMP accumulation induced by adenosine 5'-monophosphate , adenosine 5'-diphosphate , or adenosine 5'-triphosphate but not adenosine in VA-13 human fibroblasts when used at a concentration of 100 μM. Adenosine 5'-methylenediphosphate reduces proliferation of U138MG glioma cells, as well as inhibits the invasion and migration of MHCC97H hepatocellular carcinoma (HCC) cells in a migration assay.2,3It increases tumor infiltration of CD3+CD8+T cells and reduces tumor growth in a K1735 murine melanoma model when administered at a dose of 400 μg mouse.4 1.Bruns, R.F.Adenosine receptor activation by adenine nucleotides requires conversion of the nucleotides to adenosineNaunyn Schmiedebergs Arch. Pharmacol.315(1)5-13(1980) 2.Braganhol, E., Tamajusuku, A.S.K., Bernardi, A., et al.Ecto-5′-nucleotidase CD73 inhibition by quercetin in the human U138MG glioma cell lineBiochim. Biophys. Acta1770(9)1352-1359(2007) 3.Shali, S., Yu, J., Zhang, X., et al.Ecto 5′ nucleotidase (CD73) is a potential target of hepatocellular carcinomaJ. Cell Physiol.234(7)10248-10259(2018) 4.Forte, G., Sorrentino, R., Montinaro, A., et al.Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanomaJ. Immunol.189(5)2226-2233(2021)

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)

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

1(R)-(Trifluoromethyl)oleyl alcohol is an analog of oleic acid .1It inhibits ferroptosis induced by erastin in primary fibroblasts isolated from patients with Friedreich ataxia, a neuro- and cardiodegenerative disorder characterized by loss or impaired activity of frataxin (FXN), when used at concentrations of 5, 10, or 20 μM. 1(R)-(Trifluoromethyl)oleyl alcohol (5 μM) reduces lipid peroxidation induced byFXNsiRNA knockdown in NBT human myoblasts. 1.Cotticelli, M.G., Forestieri, R., Xia, S., et al.Identification of a novel oleic acid analog with protective effects in multiple cellular models of Friedreich ataxiaACS Chem. Neurosci.11(17)2535-2542(2020)

14S(15R)-EET is an oxylipin and a cytochrome P450 metabolite of arachidonic acid .114S(15R)-EET binds to isolated guinea pig monocytes with a Kivalue of 612.5 nM in a competitive binding assay using [3H]14(15)-EET.2It induces dilation of precontracted isolated canine epicardial arterioles (EC50= 4 pM) and denuded porcine subepicardial arterioles (EC50= 3 pM).3Unlike 14R(15S)-EET, 14S(15R)-EET does not inhibit COX in enzyme assays or isolated platelets.4 1.Daikh, B.E., Lasker, J.M., Raucy, J.L., et al.Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C91J. Pharmacol. Exp. Ther.271(3)1427-1433(1994) 2.Wong, P.Y.-K., Lai, P.-S., and Falck, J.R.Mechanism and signal transduction of 14 (R), 15 (S)-epoxyeicosatrienoic acid (14,15-EET) binding in guinea pig monocytesProstaglandins Other Lipid Mediat.62(4)321-333(2000) 3.Zhang, Y., Oltman, C.L., Lu, T., et al.EET homologs potently dilate coronary microvessels and activate BKCa channelsAm. J. Physiol. Heart Circ. Physiol.280(6)H2430-H2440(2001) 4.Fitzpatrick, F.A., Ennis, M.D., Baze, M.E., et al.Inhibition of cyclooxygenase activity and platelet aggregation by epoxyeicosatrienoic acidsJ. Biol. Chem.261(2)15334-15338(1986)

AZD 1152 is an orally bioavailable prodrug of AZD 1152-HQPA, a selective inhibitor of Aurora kinase B (IC50= 0.36 nM).1AZD 1152 is converted to AZD 1152-HQPA in plasma. Inhibition of Aurora B results in disruption of spindle checkpoint functions and chromosome alignment, resulting in inhibition of cytokinesis followed by apoptosis.2,3AZD 1152 inhibits tumor xenograft growthin vivo.4,5 1.Mortlock, A.A., Foote, K.M., Heron, N.M., et al.Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinaseJ. Med. Chem.50(9)2213-2224(2007) 2.Popescu, R., Heiss, E.H., Ferk, F., et al.Ikarugamycin induces DNA damage, intracellular calcium increase, p38 MAP kinase activation and apoptosis in HL-60 human promyelocytic leukemia cellsMutation Research709-71060-66(2011) 3.Moore, A.S., Blagg, J., Linardopoulos, S., et al.Aurora kinase inhibitors: Novel small molecules with promising activity in acute myeloid and Philadelphia-positive leukemiasLeukemia24(4)671-678(2010) 4.Wilkinson, R.W., Odedra, R., Heaton, S.P., et al.AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosisClin. Cancer. Res13(12)3682-3688(2007) 5.Yang, J., Ikezoe, T., Nishioka, C., et al.AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivoBlood110(6)2034-2040(2007)

Olsalazine-13C6is intended for use as an internal standard for the quantification of olsalazine by GC- or LC-MS. Olsalazine is an orally bioavailable prodrug form of the anti-inflammatory agent 5-aminosalicylic acid that is cleaved by bacterial azo reductases in the gut to generate active 5-ASA.1In vitro, olsalazine increases ion transport in isolated rabbit distal ileum when applied to the luminal side (ED50= 0.3 mM) and stimulates fluid transport in rat jejunum when used at a concentration of 5 mM.2,3Olsalazine (150 mg/kg for 8 days) improves stool consistency and decreases occult and gross bleeding as well as myeloperoxidase (MPO) activity and leukotriene B4levels in colon tissue in a mouse model of acute colitis induced by dextran sulfate .4Olsalazine also inhibits bovine xanthine oxidasein vitro(IC50= 3.4 mg/L) and lowers serum uric acid levels in a mouse model of hyperuricemia induced by oxonic acid when administered at a dose of 20 mg/kg.5Formulations containing olsalazine have been used in the treatment of inflammatory bowel disease (IBD) and ulcerative colitis. 1.Nugent, S.G., Kumar, D., Rampton, D.S., et al.Intestinal luminal pH in inflammatory bowel disease: Possible determinants and implications for therapy with aminosalicylates and other drugsGut48(4)571-577(2001) 2.Pamukcu, R., Hanauer, S.B., and Chang, E.B.Effect of disodium azodisalicylate on electrolyte transport in rabbit ileum and colon in vitro. Comparison with sulfasalazine and 5-aminosalicylic acidGastroenterology95(4)975-981(1988) 3.Mohsen, A.Q.M., Mulvey, D., Priddle, J.D., et al.Effects of olsalazine in the jejunum of the ratGut28(3)346-352(1987) 4.Murthy, S., Murthy, N.S., Coppola, D., et al.The efficacy of BAY y 1015 in dextran sulfate model of mouse colitisInflamm. Res.46(6)224-233(1997) 5.Niu, Y., Li, H., Gao, L., et al.Old drug, new indication: Olsalazine sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activityJ. Pharmacol. Sci.135(3)114-120(2017)

4'-Acetyl chrysomycin A is a bacterial metabolite and derivative of chrysomycin A that has been found inStreptomycesand has antibacterial and anticancer activities.1It is active against strains of methicillin-resistantS. aureus(MRSA) and vancomycin-resistant strains ofE. faecalisandE. faecium(MICs = 0.5-2 μg/ml for all). 4'-Acetyl chrysomycin A is cytotoxic against a panel of human cancer cell lines, including doxorubicin-sensitive or -resistant cells (IC50s = 0.085-0.26 and 3.4-16 ng/ml, respectively). 1.Wada, S.-I., Sawa, R., Iwanami, F., et al.Structures and biological activities of novel 4'-acetylated analogs of chrysomycins A and BJ. Antibiot. (Tokyo)70(11)1078-1082(2017)

Quorum sensing is a regulatory system used by bacteria for controlling gene expression in response to increasing cell density.[1] This regulatory process manifests itself with a variety of phenotypes including biofilm formation and virulence factor production.[2] Coordinated gene expression is achieved by the production, release, and detection of small diffusible signal molecules called autoinducers. The N-acylated homoserine lactones (AHLs) comprise one such class of autoinducers, each of which generally consists of a fatty acid coupled with homoserine lactone (HSL). Regulation of bacterial quorum sensing signaling systems to inhibit pathogenesis represents a new approach to antimicrobial therapy in the treatment of infectious diseases.[3] AHLs vary in acyl group length (C4-C18), in the substitution of C3 (hydrogen, hydroxyl, or oxo group), and in the presence or absence of one or more carbon-carbon double bonds in the fatty acid chain. These differences confer signal specificity through the affinity of transcriptional regulators of the LuxR family.[4] C16-HSL is one of a number of lipophilic, long acyl side-chain bearing AHLs, including its monounsaturated analog C16:1-(L)-HSL, produced by the LuxI AHL synthase homolog SinI involved in quorum-sensing signaling in S. meliloti, a nitrogen-fixing bacterial symbiont of certain legumes.[5],[6] C16-HSL is the most abundant AHL produced by the proteobacterium R. capsulatus and activates genetic exchange between R. capsulatus cells.[7] N-Hexadecanoyl-L-homoserine lactone and other hydrophobic AHLs tend to localize in relatively lipophilic cellular environments of bacteria and cannot diffuse freely through the cell membrane. The long-chain N-acylhomoserine lactones may be exported from cells by efflux pumps or may be transported between communicating cells by way of extracellular outer membrane vesicles.[8],[9]Reference:[1]. González, J.E., and Keshavan, N.D. Messing with bacterial quorum sensing Microbiol. Mol. Biol. Rev. 70(4), 859-875 (2006).[2]. Gould, T.A., Herman, J., Krank, J., et al. Specificity of acyl-homoserine lactone syntheses examined by mass spectrometry Journal of Bacteriology 188(2), 773-783 (2006).[3]. Cegelski, L., Marshall, G.R., Eldridge, G.R., et al. The biology and future prospects of antivirulence therapies Nature Reviews.Microbiology 6(1), 17-27 (2008).[4]. Penalver, C.G.N., Morin, D., Cantet, F., et al. Methylobacterium extorquens AM1 produces a novel type of acyl-homoserine lactone with a double unsaturated side chain under methylotrophic growth conditions FEBS Letters 580, 561-567 (2006).[5]. Gao, M., Chen, H., Eberhard, A., et al. sinI- and expR-dependent quorum sensing in Sinorhizobium meliloti Journal of Bacteriology 187(23), 7931-7944 (2005).[6]. Teplitski, M., Eberhard, A., Gronquist, M.R., et al. Chemical identification of N-acyl homoserine lactone quorum-sensing signals produced by Sinorhizobium meliloti strains in defined medium Archives of Microbiology 180, 494-497 (2003).[7]. Schaefer, A.L., Taylor, T.A., Beatty, J.T., et al. Long-chain acyl-homoserine lactone quorum-sensing regulation of Rhodobacter capsulatus gene transfer agent production Journal of Bacteriology 184(23), 6515-6521 (2002).[8]. Pearson, J.P., Van Delden, C., and Iglewski, B.H. Active efflux and diffusion are involved in transport of Pseudomonas aeruginosa cell-to-cell signals Journal of Bacteriology 181(4), 1203-1210 (1999).[9]. Mashburn-Warren, L., and Whiteley, M. Special delivery: Vesicle trafficking in prokaryotes Molecular Microbiology 61(4), 839-846 (2006).

Betamethasone 21-phosphate is a synthetic glucocorticoid.1It prevents increases in macrophage and eosinophil numbers in bronchoalveolar lavage fluid (BALF) and decreases in blood leukocyte numbers in a guinea pig model of parainfluenza-3 viral infection when administered at a dose of 8 mg/kg but does not prevent airway hyperresponsiveness after infection.2Betamethasone 21-phosphate inhibits cell infiltration into the aqueous humor in a rat model of endotoxin-induced uveitis when administered topically or subcutaneously at doses of 0.01-1% or 1 mg/kg, respectively.3It increases maximal lung pressure volume curves in fetal sheep when administered to pregnant ewes at 0.75 gestation at doses of 80 and 170 μg/kg.1Betamethasone 21-phosphate increases body weight, impairs learning and memory, increases anxiolytic behavior, and reduces hippocampal neurogenesis in CD-1 mice but reduces body weight and increases neurogenesis with no effect on anxiety in high-anxiety DBA/2 mice when administered at a dose of approximately 25 mg/kg per day in the drinking water for seven weeks.4Formulations containing betamethasone 12-phosphate and betamethasone acetate have been used in the treatment of severe allergic conditions and a variety of immune-related conditions. 1.Loehle, M., Schwab, M., Kadner, S., et al.Dose-response effects of betamethasone on maturation of the fetal sheep lungAm. J. Obstet. Gynecol.202(2)186.e181-186.e187(2010) 2.Leusink-Muis, A., Ten Broeke, R., Folkerts, G., et al.Betamethasone prevents virus-induced airway inflammation but not airway hyperresponsiveness in guinea pigsClin. Exp. Allergy29(Suppl. 2)82-85(1999) 3.Tsuji, F., Sawa, K., Kato, M., et al.The effects of betamethasone derivatives on endotoxin-induced uveitis in ratExp. Eye Res.64(1)31-36(1997) 4.Aiello, R., Crupi, R., Leo, A., et al.Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesisBehav. Brain Res.278155-166(2015)

Collinin is a coumarin that has been found in Z. schinifolium and has diverse biological activities.1,2,3,4 It is active against drug-susceptible and -resistant strains of M. tuberculosis (MIC50s = 3.13-6.25 μg/ml).1 Collinin inhibits LPS-induced nitric oxide (NO) production (IC50 = 5.9 μM) and reduces COX-2 protein levels in RAW 264.7 cells.2 It completely inhibits aggregation of isolated rabbit platelets induced by arachidonic acid , collagen, or platelet activating factor (PAF) when used at a concentration of 100 μM.3 Dietary administration of collinin (0.05% w/w) reduces the number of mice with tumors and the number of tumors per mouse in a mouse model of colitis-related carcinogenesis.4 |1. Kim, S., Seo, H., Al Mahmud, H., et al. In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis. Phytomedicine 46, 104-110 (2018).|2. Nguyen, P.-H., Zhao, B.T., Kim, O., et al. Anti-inflammatory terpenylated coumarins from the leaves of Zanthoxylum schinifolium with α-glucosidase inhibitory activity. J. Nat. Med. 70(2), 276-281 (2016).|3. I.S., C., Lin, Y.C., Tsai, I.L., et al. Coumarins and anti-platelet aggregation constituents from Zanthoxylum schinifolium. Phytochemistry 39(5), 1091-1097 (1995).|4. Kohno, H., Suzuki, R., Curini, M., et al. Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice. Int. J. Cancer 118(12), 2936-2942 (2006).

(R)-(+)-Blebbistatin O-Benzoate is a derivative of Blebbistatin. (R)-(+)-Blebbistatin is a 1-phenyl-2-pyrrolidinone derivative and a selective inhibitor of non-muscle myosin II. It blocks cell blebbing rapidly and reversibly and also disrupts directed cell migration and cytokinesis in vertebrate cell. (R)-(+)-Blebbistatin can also inhibit contraction of the cleavage furrow without disrupting mitosis or contractile ring assembly. (R)-(+)-Blebbistatin is suitable as a negative control for (S)-(-)-Blebblastatin.

Hepatitis B Virus Pre-S Region (120-145) is a preS2 peptide that effectively blocks the attachment of single-chain Fv fragment (scFv) or IgG to recombinant Hepatitis B surface antigen (r-HBsAg) [1].

19(R)-Hydroxylated prostaglandins (PGs) are present at µg/ml concentrations in the semen of some mammalian species, notably primates, with the majority being from the PGE series and featuring a 15(S),19(R) hydroxyl stereochemistry. These compounds are also observed in marsupials' seminal plasma, where F-type 1 and 2-series compounds are predominant. The 15(R)-hydroxy epimer represents the inverse or unnatural isomer at C-15 for these 19-hydroxylated PGs. Although the biological function of 19(R)-hydroxylated PGs remains unclear, 19(R)-hydroxylation in the F-series leads to a notable reduction in receptor-mediated biological activity in certain assays.