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  • before people said there is no cure on HIV/AIDS but today many people have now believe that there is a cure. HIV/AIDS can be cured through Africans root and herbs,and days our great doctors have finally found the cure of HIV/AIDS, many have get cured with the help of a great spell caster known as dr okoror he is the one of the great spell doctor in Africa and he has the cure on this disease HIV/AIDS. last month he share is Haber medicine in some medical hospital and now he is well recognize as one of the best spell caster in Africa, you don't have to be sad any more or share your tears any more on this disease when the cure have already be found. in 2013 the total number of people living with HIV/AIDS was 12.9 million but today the total number is 1.6 million if you want to get in touch with him contact him on this e-mail below:(okororspell@outlook.com )
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TOPIX

  1. 1. TOPIX NEWSLETTER Issue 3/2010 Cell Death, Cancer & Immunology Fas Ligands 2 Apoptosis Detection Kits 3 Methionine Aminopeptidase 2 4 CDC25 4-5 Deubiquitinylating Enzymes 5 Compound Corner 6-7 [NKT Cell Activators, Geldanamycin Analogs] New Antibodies 8-9 [BAFF; CEACAM; GPCRs; HSPs; LC3] CD40/CD40L 10 Cytokine Kits 11 New Dkk-1 Products 12 International Edition
  2. 2. 2 Fas Ligands Fas (CD95; APO-1; TNFRSF6) is a member of the tumor necrosis factor (TNF) receptor superfamily and is an important media- tor of apoptotic cell death. Binding of the Fas ligand (FasL; CD95L; APO-1L; TNFSF6; CD178) to Fas induces the formation of the death-inducing signaling complex (DISC). The DISC consists of trimerized Fas, the death domain (DD) containing adapter molecule Fas-associated DD (FADD), procaspase-8a (FLICE; MACH1; MCH5), procaspase-8b (MACH2), procaspase-10 and the cellular FLIP (FADD-like interleukin-1β-converting enzyme inhibitory protein) proteins. The formation of the DISC results in the autoproteolytic cleavage of procaspase-8 and procaspase-10 and ultimately induces apoptosis. Fas-induced apoptosis can be effectively blocked at several stages by either FLICE-inhibitory protein (FLIP), by Bcl-2, or by the cytokine response modifier A (CrmA). In addition to its role in apoptosis, Fas signaling plays a critical role in the immune system where it mediates killing of pathogen-infected cells and the death of obsolete and potentially dangerous lymphocytes. FasL [CD95L; TNFSF6; CD178] The Standard Apoptosis Inducer! FasL (soluble) (human), (rec.) Fas (human), mAb (APO-1-3) ALX-522-001-C010 10 µg ALX-805-020-C100 Purified 100 µg ALX-522-001-3010 SuperPack 3 x 10 µg CLONE: APO-1-3. ISOTYPE: Mouse IgG3. IMMUNOGEN: Human recombinant Fas (CD95; APO-1). SPECIFICITY: Recognizes human Fas. APPLICATION: FC, Produced in HEK 293 cells. The extracellular domain of human FasL (APO- IP, WB. 1L; CD95L; CD178) (aa 103-281) is fused at the N-terminus to a linker peptide (26 aa) and a FLAG®-tag. Glycosylation of rhsFasL is similar to that of natural human FasL. SPECIFICITY: Binds to human, mouse and rat Fas (CD95; APO-1). BIOLOGICAL ACTIVITY: Kills Jurkat cells at concentrations Key Antibodies to FLIP of >10ng/ml in the absence of a cross-linker. Cross-linking enhancer (see Set Prod. No. ALX-850-014) increases the activity of rhsFasL approx. 50- FLIP, mAb (Dave-2) fold. ATTENTION: Results using sFasL may differ from those obtained with ALX-804-127-C100 100 µg agonistic antibodies! CLONE: Dave-2. ISOTYPE: Rat IgG2a. IMMUNOGEN: Recombinant human LIT: Agonist antibody and Fas ligand mediate different sensitivity to death in the signaling pathways of Fas and cytoplasmic mutants: A.R. Thilenius, et al.; Eur. J. Immunol. 27, 1108 (1997)  T cell FLIP (aa 1-480). SPECIFICITY: Recognizes an epitope (aa 1-200) present costimulation by the TNF ligand BAFF: B. Huard, et al.; J. Immunol. 167, 6225 (2001)  Loss of in both short (FLIPS) and long (FLIPL) splice variants of human and mouse the BH3-only protein Bmf impairs B cell homeostasis and accelerates gamma irradiation-induced thymic lymphoma development: V. Labi, et al.; J. Exp. Med. 205, 641 (2008)  For a comprehensive FLIP. APPLICATION: IP, WB. bibliography please visit our website. FLIP (human), mAb (NF6) FasL (soluble) (human), (rec.) set ALX-804-428-C050 50 µg ALX-850-014-KI02 1 Set ALX-804-428-C100 100 µg SET CONTAINS: CLONE: NF6. ISOTYPE: Mouse IgG1. IMMUNOGEN: Recombinant human • 10 µg of FasL (soluble) (human), (rec.) (Prod. No. ALX-522-001) FLIP (aa 1-194). SPECIFICITY: Recognizes short (FLIPS) and long (FLIPL) • 4 x 50 µg of Enhancer for Ligands (Prod. No. ALX-804-034) which in- splice variants of human FLIP. APPLICATION: WB. creases the biological activity (induction of apoptosis) by ~50-fold to a concentration range of 1-5ng/ml. Fas Signaling BIOLOGICAL ACTIVITY: Kills Fas-sensitive cells at concentrations of >1ng/ Our Caspase-8 Gold Standards! ml in the presence of cross-linking enhancer. SPECIFIC ACTIVITY: ED50: 1ng/ ml (A20 cells). Caspase-8 (human), mAb (12F5) LIT: Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl- 2 or Bcl-x(L): D.C. Huang, et al.; PNAS 96, 14871 (1999)  NF-κB signals induce the expression ALX-804-242-C100 100 µg of c-FLIP: O. Micheau, et al.; Mol. Cell. Biol. 21, 5299 (2001)  Caspase-10 is recruited to and activated at the native TRAIL and CD95 death-inducing signalling complexes in a FADD-depend- CLONE: 12F5. ISOTYPE: Mouse IgG2b. IMMUNOGEN: Recombinant human cas- ent manner but can not functionally substitute caspase-8: M.R. Sprick, et al.; EMBO J. 21, 4520 pase-8. SPECIFICITY: Recognizes human procaspase-8 and active human (2002)  The role of p53 and Fas in a model of acute murine graft-versus-host disease: S. Yada, et al.; J. Immunol. 174, 1291 (2005)  Amplification of CD95 activation by caspase 8-induced en- caspase-8. Detects procaspase-8 (p55/54), the intermediate cleavage prod- dosomal acidification in rat hepatocytes: R. Reinehr, et al.; J. Biol. Chem. 283, 2211 (2008)  For ucts (p43/41) and the p18 active subunit of caspase-8 by Western blot. Does a comprehensive bibliography please visit our website. not recognize mouse caspase-8. APPLICATION: IP, WB. SuperFasLigand™ (soluble) (human), (rec.) ALX-522-020-C005 5 µg ALX-522-020-3005 SuperPack 3 x 5 µg FIGURE: Detection of Fas ligand-induced cas- pase-8 processing and activation in human Jurkat Produced in HEK 293 cells. The extracellular domain of human FasL cells. (APO-1L; CD95L; CD178) (aa 103-281) is fused at the N-terminus to METHOD: Jurkat cells were treated with Fas lig- a linker peptide (26 aa) and a FLAG®-tag. Glycosylation of rhsSuper- and (100ng/ml). FasLigandTM is similar to natural human FasL. SPECIFICITY: Binds to human, mouse and rat Fas (CD95; APO-1). BIOLOGICAL ACTIVITY: Kills Fas-sensitive cells at concentrations of >1ng/ml. NOTE: Does not re- Caspase-8 (mouse), mAb (1G12) quire an enhancer. LIT: Fas ligand (CD95L) protects neurons against perforin-mediated T lymphocyte cytotoxicity: ALX-804-447-C100 100 µg I. Medana, et al.; J. Immunol. 167, 674 (2001)  Tumor-cell resistance to death receptor-induced CLONE: 1G12. ISOTYPE: Rat IgG1. IMMUNOGEN: Recombinant mouse cas- apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax: H. LeBlanc, et al.; Nat. Med. 8, 274 (2002)  Inhibition of metalloproteinase cleavage enhances the cyto- pase-8 p18 subunit. SPECIFICITY: Recognizes the p18 subunit of mouse toxicity of Fas ligand: P.G. Knox, et al.; J. Immunol. 170, 677 (2003)  In vitro engagement of caspase-8. Detects bands of ~55kDa (full-length caspase-8) and ~18kDa CD3 and CD28 corrects T cell defects in chronic lymphocytic leukemia: M. Bonyhadi, et al.; J. Immunol. 174, 2366 (2005)  For a comprehensive bibliography please visit our website. (apoptosis-induced cleavage fragment) by Western blot. Does not cross- react with human caspase-8. APPLICATION: ELISA, FC, ICC, WB. www.enzolifesciences.com
  3. 3. 3 Apoptosis Detection Kits Apoptosis Biomarker Assays for Clinical Diagnostics and Research The M30-Apoptosense® and M65® ELISA assays discrimi- nate between different modes of epithelial cell death by quantitative measurement of either the full-length cytok- eratin 18 (CK18) protein or one of the caspase-cleaved fragments of CK18 (ccCK18/CK18F). The M30-Apoptosense® ELISA assay utilizes the M5 capture antibody and the M30 CytoDEATHTM antibody (ALX-804-590) to detect CK18 fragments containing neo- epitopes (NE) at positions 387-396, which are generated during the early stages of apoptosis by the action of cas- pases-3, -7 and -9. The M65® ELISA also detects cleaved fragments, however, it uses a different detection antibody from M30, namely M5, that does not distinguish between the full-length protein and its fragments. Thus, the M65® ELISA measures both caspase-cleavage (apoptosis) and cellular release of intact CK18 (necrosis). Since both assays utilize the same recombinant CK18 protein fragment as a reference, the ratio of M65/M30 potentially becomes a readout, which provides additional information on the predominant mode of (tumor) cell death. These assays have been used in multiple pre-clinical and clinical research applications, but increasingly, are being used used as exploratory pharmacodynamic endpoints in clinical trials with apoptosis-modulating therapies. Product Prod. No. Size M30-Apoptosense ELISA kit ® ALX-850-270-KI01 1 Kit ALX-850-270-5001 5 x 1 Kit M65® ELISA kit ALX-850-310-KI01 1 Kit Apoptosis Detection Kits M30 CytoDEATHTM ELISA kit NEW ALX-850-336-KI01 1 Kit The novel M30 CytoDEATH™ ELISA is designed as a high-throughput assay for functional screening and in vitro characterization of pro-apoptotic drugs using cell culture supernatants, and spheroid or tissue lysates (as it detects an intracellular physiological caspase substrate: CK18). Cell Death Assays for Flow Cytometry or Microscopy GFP-Certified™ Apoptosis/Necrosis detection kit Nuclear-ID™ Green chromatin condensation ENZ-51002-25 25 Assays detection kit ENZ-51002-100 100 Assays ENZ-51021-K200 200 Assays Specifically designed for use with GFP-expressing cell lines and cells ex- Provides a rapid and convenient assay for one of the more prominent hall- pressing blue or cyan fluorescent proteins (BFPs, CFPs). The kit includes all marks of apoptosis, nuclear condensation. The kit contains a DNA interca- the necessary reagents for determination of early and late stages of apop- lating dye that brightly stains the condensed chromatin of apoptotic cells, tosis as well as necrosis. It is suitable for use with live or post-fixed cells but only dimly stains the normal chromatin of live cells. This staining pattern in conjunction with probes, such as labeled antibodies, or other fluorescent makes it possible to distinguish between healthy and apoptotic cell popula- conjugates displaying similar spectral properties as fluorescein or coumarin. tions by fluorescence microscopy or flow cytometry. Additionally, it provides quick and accurate results via flow cytometry and fluorescence/confocal microscopy. LIT: Cell Surface Externalization of Annexin A1 as a Failsafe Mechanism Preventing Inflammatory Responses during Secondary Necrosis: K.E. Blume, et al.; J. Immunol. 183, 8138 (2009), Sup- plemental Information C A FIGURE: GFP-expressing cell line stained with GFP- Certified™ Apoptosis/ Control 10µM β-Lapachone Necrosis Detection System 50µM BML-258 A: Viable cells FIGURE: Monitoring chromatin condensation arising from the application of an ap- B: Early apoptotic cells optosis inducing agent. Jurkat cells (1x 106 cells/ml) were treated with the indicated B C: Late apoptotic cells drug for 4 hours. The flow cytometry study demonstrates the potential of using the D D: Necrotic cells assay for drug screening. Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation; IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide International Edition
  4. 4. 4 Methionine Aminopeptidase 2 (MetAP2) MetAP2 is a metalloenzyme that catalyzes removal of the N-terminal methionine from proteins, with the physiologically relevant metal thought to be either cobalt or manganese. Since it was identified as a target of the antiangiogenic natural product fumagillin (Prod. No. BML-CT100), it has been studied for its involvement Methionine Aminopeptidase 2 (MetAp2) in cancer, angiogenesis, inflammation, and rheumatoid arthritis. Because of differing substrate specificities and kinetics, it is not desirable to substitute FIGURE: Structural representation of human bacterial methionine aminopeptidase MetAP2 complexed with inhibitor A797859 for mammalian MetAP2. (MMDB ID: 62187). Fumagillin Met-AMC (fluorogenic substrate) BML-CT100-0001 1 mg BML-P236-0025 25 mg BML-CT100-0005 5 mg Fluorogenic substrate for methionine aminopeptidase 2 (MetAP2) (kcat/ Inhibitor of angiogenesis and endothelial cell proliferation. Specific inhibi- Km=1.1 x 10 M-1min-1; Km=310 µM) or aminopeptidase N (Km=377µM). tor of methionine aminopeptidase type 2 (MetAP2) by covalently modifying Ex.: 380nm, Em.: 460nm, although the following Ex/Em can also be used: a conserved active-site histidine. Precursor to TNP-470. Exhibits antitu- 355,375/440,450. This substrate is useful for inhibitor screening and ki- mor activity in estrogen-induced pituitary adenoma. Antineoplastic. Anti- netic analysis. infective. LIT: The anti-angiogenic agent fumagillin covalently MetAP2 (human), (rec.) (GST-tag) binds and inhibits the methionine aminopeptidase, BML-SE538-0010 10 µg MetAP-2: N. Sin, et al.; PNAS 94, 6099 (1997)  The anti-angiogenic agent fumagillin covalently modifies Recombinant full-length (aa 1-478) methionine aminopeptidase 2 (MetAP2; a conserved active-site histidine in the Escherichia coli methionine aminopeptidase: W.T. Lowther, et p67eIF2; Eukaryotic initiation factor 2-associated protein), cloned from hu- al.; PNAS 95, 12153 (1998)  Molecular recognition man cDNA (NM_006838), expressed in insect cells, and purified using an of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2: E.C. Griffith, et al.; N-terminal GST tag. PNAS 95, 15183 (1998) CDC25 CDC25 protein tyrosine phosphatases dephosphorylate and activate cyclin dependent kinases, thus promoting cell division. All three of the genes encoding the CDC25 phosphatases are considered potential oncogenes and the enzymes are drug discovery targets. CDC25 CDC25 Enzymes Active, full-length CDC25s expressed in E. coli. Ideal for kinetic studies and inhibitor screening. Product Prod. No. Size CDC25A (human), (rec.) BML-SE364-0050 50 µg CDC25B (human), (rec.) BML-SE365-0050 50 µg CDC25C (human), (rec.) BML-SE366-0050 50 µg CDC25 Antibody CDC25A, mAb (DCS-120) ADI-KAM-CC085-E 100 µg CLONE: DCS-120. ISOTYPE: Mouse IgG2. IMMUNOGEN: Recombinant human CDC25A CDC25A protein. SPECIFICITY: Recognizes human, mouse and rat CDC25A. FIGURE: Western blot analysis of human APPLICATION: IP, WB. HeLa cell lysate (1), mouse N1H/T3 cell lysate (2), and rat Rat-1 cell lysate (3), probed with KAM-CC085. www.enzolifesciences.com
  5. 5. 5 CDC25 Inhibitors Artesunate NSC-95397 BML-PR117-0010 10 mg BML-EI309-0005 5 mg BML-PR117-0050 50 mg BML-EI309-0025 25 mg Artesunate is a semisynthetic derivative of artemisinin. In addition to its well A potent and selective inhibitor of CDC25 phosphatase (Ki's for CDC25A, B known antimalarial activity, it displays a profound cytotoxic action against and C are 32, 96 and 40 nM respectively). NSC-95397 inhibits the growth of fifty-five tumor cell lines. The molecular mode of action of artesunate in- several human tumor cell lines and blocks G2/M cell cycle transition. CDC25 volves down-regulation of CDC25A. LIT: Identification of a potent and selective pharmacophore for Cdc25 dual specificity phosphatase inhibitors.: J.S. Lazo, et al.; LIT: Molecular modes of action of artesunate in tumor cell Mol. Pharmacol. 61, 720 (2002) lines: T. Efferth, et al.; Mol. Pharmacol. 64, 382 (2003) Deubiquitinylating Enzymes (DUBs) and Cancer Deubiquitinylating Enzymes (DUBs) and Cancer Mammals contain some 80-90 DUBs in five different subfamilies, only a small number of which have been characterized with A Potent and Specific Inhibitor respect to the proteins that they interact with and deubiquitinylate. Several human DUBs are direct antagonists of oncogenic or Ubiquitin aldehyde (rec.) tumor-suppressive E3 ligases and are increasingly being seen BML-UW8450-0050 50 µg as potential targets in cancer therapies. Promising candidates A potent, highly specific inhibitor of ubiquitin deconjugating enzymes, in- include the nuclear DUBs, USP1, USP7 and USP28, which all cluding all UCH and USP family members. Co-crystallization of ubiquitin control processes relevant to cancer. Specifically, USP1 has aldehyde with specific deubiquitinylating enzymes has also been used to been shown to modulate DNA-repair checkpoints, whilst USP7 probe enzyme:substrate interactions. plays key roles in the p53 pathway (whereby it stabilizes both p53 and Hdm2) and USP28 is overexpressed in colon and breast tumors. Other DUBs have been shown to regulate the Active Site-directed Probes NF-κB signaling pathway, which is under the control of CYLD, a tumor-suppressor gene mutated in skin tumors. With reduced Ubiquitin vinyl sulfone, (HA-tag) expression also found in tumors of the liver and kidney, it is BML-UW0155-0025 25 µg possible that CYLD may have a more general role as a tumor A useful reagent for the detection and identification of DUBs. HA-Ub-VS acts suppressor. as a potent and irreversible inhibitor of DUBs through covalent modification LIT: Targeting the ubiquitin system in cancer therapy: D. Hoeller and I. Dikic; Nature. 458, 438 (2009)  Deubiquitylating enzymes and disease: S. Singhal, et al.; BMC Biochem. 9 Suppl. 1, S3 of the active site, and as a specific probe for enzymes with DUB activity. (2008)  Protein partners of deubiquitinating enzymes: K.H. Ventii & K.D. Wilkinson; Biochem. J. 414, 161 (2008) A Sensitive Fluorogenic Substrate HAUbVS-UCHL1 HAUbVS-USP2cd FIGURE: DUB active site probe assay: Ubiquitin-AMC MW (KDa) Western blot showing reactions containing HAUbVS only (lane 1), HAUbVS + USP2cd BML-SE211-0025 25 µg (lane 2, Prod. No.BML-UW9850), and A fluorogenic substrate for a wide range of DUBs, including ubiquitin C- HAUbVS + GSTUCHL1 (lane 3, Prod. No. BML-UW9305), HAUbVS modifi ed proteins terminal hydrolases (UCHs) and ubiquitin specific proteases (USPs). It is detected using HA-reactive polyclonal HAUbVS a useful reagent for the study of deubiquitinylating activity where detec- antibody (Sigma - H6908) at 1:2000 tion sensitivity or continuous monitoring of activity is essential. dilution. Also available: Product Prod. No. Size Ubiquitin vinyl methyl ester, (HA-tag) BML-UW0880-0025 25 µg Chloroethyl ubiquitin, (HA-tag) BML-UW0885-0025 25 µg Bromoethyl ubiquitin, (HA-tag) BML-UW0890-0025 25 µg Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation; IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide International Edition
  6. 6. 6 Compound Corner NKT Cell Activators a-GalCer was the first defined and most potent agonistic antigen of the natural killer T cell (NKT) T cell receptor (TCR). De- rivatives of a-GalCer stimulate the production of smaller amounts of IFN-g than a-GalCer, but induce equal or greater IL-4 secretion in mouse models. a-GalCer Analog 7 NEW ALX-306-032-C500 500 µg a-GalCer Analog 8 NEW ALX-306-033-C500 500 µg LIT: Synthesis and evaluation of 1,2,3-triazole containing analogues of the immunostimulant a-GalCer: T. Lee, et al.; J. Med. Chem. 50, 585 (2007) a-GalCer Analog 7 KRN7000 [a-Galactosylceramide; a-GalCer] BML-SL232-0100 100 µg BML-SL232-1000 1 mg KRN7000 is a synthetic analog of a-galactosylceramide and the marine natural product agelasphin. It is a specific ligand for human and mouse NKT a-GalCer Analog 8 cells and remains the best studied ligand of the lipid-binding MHC class I- like protein CD1d. It protects against LPS-induced shock and displays po- tent antitumor activity in various in vivo models. HO OH O LIT: A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with O advanced and recurrent non-small cell lung cancer: A. Ishikawa, et al.; Clin. Cancer Res. 11, 1910 C24H49 HO HN (2005)  Production and characterization of monoclonal antibodies against complexes of the NKT HO OH cell ligand alpha-galactosylceramide bound to mouse CD1d: K.O. Yu, et al.; J. Immunol. Methods O 323, 11 (2007)  For a comprehensive bibliography please visit our website. C14H29 Isoglobotrihexosylceramide KRN7000 [a-GalCer] OH [iGb3] ALX-306-028-C100 100 µg ALX-306-028-M001 1 mg Lysosomal glycosphingolipid proposed to be the natural ligand of NKT cells. Stimulates natural killer T (NKT) cells similar to a-GalCer. For negative control compound see globotrihexosylceramide (Gb3) (Prod. No. ALX-306-030). Compound Corner LIT: Lysosomal glycosphingolipid recognition by NKT cells: D. Zhou, et al.; Science 306, 1786 (2004) Isoglobotrihexosylceramide  Synthesis and biological evaluation of alpha-galactosylceramide (KRN7000) and isoglobotrihex- osylceramide (iGb3): C. Xia, et al.; Bioorg. Med. Chem. Lett. 16, 2195 (2006)  Chemoenzymatic Syntheses of iGb3 and Gb3: Q. Yao, et al.; Org. Lett. 8, 911 (2006) HIF-1a Modulators Dimethyl-bisphenol A BML-GR339-0010 10 mg BML-GR339-0050 50 mg Promotes degradation of HIF-1a. LIT: Bisphenol A, an environmental endocrine-disrupting chemical, inhibits hypoxic response via degradation of hypoxia-inducible factor 1alpha (HIF-1alpha): structural requirement of bisphenol A for degradation of HIF-1alpha: T. Kubo, et al.; BBRC 318, 1006 (2004) Dimethyl-bisphenol A Dimethyloxaloylglycine BML-EI347-0010 10 mg BML-EI347-0050 50 mg DMOG is a cell permeable prolyl-4-hydroxylase inhibitor which upregulates HIF activity. HIF activation stimulates angiogenesis in several different models. DMOG also inhibits FIH (Factor Inhibiting HIF), an asparaginyl hydroxylase, which enhances the HIF response. It is active in vivo and attenuates myocardial injury in a rabbit ischemia reperfusion model (20mg/kg). Expected to be pro- angiogenic. Dimethyloxaloylglycine LIT: Stimulation of HIF-1alpha, HIF-2alpha, and VEGF by prolyl 4-hydroxylase inhibition in human lung endothelial and epithelial cells: T.M. Asikainen, et al.; Free Radic. Biol. Med. 38, 1002 (2005)  Activation of hypoxia-inducible factors in hyperoxia through prolyl 4-hydroxylase blockade in cells and explants of primate lung: T.M. Asikainen, et al.; PNAS 102, 10212 (2005) www.enzolifesciences.com
  7. 7. 7 Geldanamycin Analogs 17-AAG 17-DMAG BML-EI308-0001 1 mg BML-EI337-0001 1 mg 17-AAG is a less toxic and more stable analog of geldanamycin (Prod. No. Less toxic, more potent synthetic derivative of geldanamycin (Prod. No. BML- BML-EI280). Inhibitor of heat shock protein 90 (HSP90) that displays a 100- EI280). Inhibitor of angiogenesis. Inhibitor of heat shock protein 90 (HSP90). fold higher affinity for HSP90 derived from tumor cells compared to HSP90 Cytotoxic against multiple cancer cell types and inhibits angiogenesis. In- from normal cells. 17-AAG inhibits Akt activation and expression in tu- ducer of apoptosis with higher antitumor activity than 17-AAG (Prod. No. mors and synergizes with a number of antitumor BML-EI308). 17-DMAG or geldanamycin agents such as taxol, cisplatin, and UCN-014. reduces the uptake of chaperone medi- 17-AAG causes the inactivation, destabilization ated autophagy (CMA) substrates by iso- and eventual degradation of HIF-1a. Inhibitor of lated lysosomes. telomerase activity. Inducer of apoptosis with an- LIT: Enhanced tumor cell radiosensitivity and abroga- tion of G2 and S phase arrest by the Hsp90 inhibi- titumor activity. Inducer of macroautophagy. tor 17-(Dimethylaminoethylamino)-17-demethoxy- LIT: A high-affinity conformation of Hsp90 confers tumour se- geldanamycin: E.E. Bull, et al.; Clin. Cancer Res. 10, lectivity on Hsp90 inhibitors: A. Kamal, et al.; Nature 425, 407 8077 (2004) (2003) Ionophore Antibiotics Enniatins belong to a family of depsipeptides produced by several species of Fusarium. Enniatins have been shown to act as ionophores. Potential anticancer compounds. LIT: Ionophore antibiotics produced by the fungus Fusarium orthoceras var. enniatum and other Fusaria: E. Gaumann, et al.; Experientia 3, 202 (1947)  Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic activities against human cancer cells: R. Dornetshuber, et al.; Chem. Res. Toxicol. 20, 465 (2007)  Enniatins A1, B and B1 from an endophytic strain of Fusarium tricinctum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation: W. Wätjen et al.; Mol. Nutr. Food Res. 53, 431 (2009)  For a comprehensive bibliography please visit our website. Product Isolated from Prod. No. Size Enniatin A Fusarium sp. ALX-380-310-MC05 0.5 mg Enniatin A1 Fusarium sp. ALX-380-311-M001 1 mg Enniatin B Fusarium orthoceras var. enniatum. ALX-380-007-M001 1 mg Enniatin B1 Fusarium sp. ALX-380-312-M001 1 mg Compound Corner Enniatin A Enniatin A1 Enniatin B Enniatin B1 Latest Insight A recent publication by Houghton et al., demonstrates that neutrophil elastase acts through a unique intracellular mecha- nism to promote tumorigenesis. By examining neutrophil elastase localization, the authors found that the secreted enzyme is internalized by epithelial tumor cells, where it degrades the adapter IRS-1. This, in turn, frees PI 3-kinase to transduce pro-mitotic signals from the PDGF receptor. The study is of interest, not only for introducing a unique non-cell autonomous, intracellular mechanism for neutrophil elastase, but it also provides a potentially novel therapeutic ap- proach to lung cancer using anti-inflammatory drugs, in particular neutrophil elastase inhibitors. The authors show that the neutrophil elastase inhibitor sivelestat (BML-PI157), a drug approved in Japan, shows antitumor efficacy in mice. LIT: Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth: A.M. Houghton et al.; Nat. Med. 16, 219 (2010) Sivelestat sodium Elasnin BML-PI157-0010 10 mg ALX-350-171-M001 1 mg BML-PI157-0050 50 mg ALX-350-171-M005 5 mg LIT: ONO-5046, a novel inhibitor O O LIT: Inhibition of human leukocyte of human neutrophil elastase: K. elastase, porcine pancreatic elastase, S Kawabata, et al.; BBRC 177, 814 O N and chymotrypsin by elasnin and other (1991) H 4-hydroxy-2-pyrones: R.W. Spencer, et H3C O-Na+ al.; J. Med. Chem. 28, 1828 (1985) O O N H3C H CH3 O Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation; IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide International Edition
  8. 8. 8 New Antibodies CEACAMs CD5L CEA-related cell adhesion molecules (CEACAM) belong Human CD5L (Spa; API6) inhibits tumor necrosis factor-a to the carcinoembryonic antigen (CEA) family. It consists secretion by human monocytes stimulated with LPS or LTA. of seven CEACAM (CEACAM1, CEACAM3 - CEACAM8) Binding of CD5L to conserved components of bacterial sur- and 11 pregnancy-specific glycoprotein (PSG1 - PSG11) faces and modulation of the monocyte response indicate that members which function as cell adhesion molecules, tumor this molecule is an active constituent of the innate immune suppressors, regulators of lymphocytes, activators of dendritic response of the host. cells, and receptors of Neisseria species and other bacteria. Overexpression of CEA/CEACAM5 in tumors of epithelial CD5L, mAb (9F3b) origin is the basis of its wide-spread use as a tumor marker. ALX-803-336-C100 100 µg CLONE: 9F3b. ISOTYPE: Mouse IgG1. IMMUNOGEN: Recombinant human CD5L. CEACAM5,6 (human), mAb (MUS) SPECIFICITY: Recognizes human and mouse CD5L. APPLICATION: IP, WB, ELISA. ALX-805-086-C100 100 µg CLONE: MUS. ISOTYPE : Mouse IgG1. IMMUNOGEN : Extracted human CEACAM5. CD5L (human), mAb (3B1a) SPECIFICITY : Recognizes human CEACAM5 and 6. Does not cross-react with ALX-803-337-C100 100 µg human CEACAM1, 3, 4, 7 or 8. APPLICATION : FC, ELISA, IHC (FS), WB. CLONE: 3B1a. ISOTYPE: Mouse IgG2. IMMUNOGEN: Recombinant human CD5L. SPECIFICITY: Recognizes human CD5L. APPLICATION: IP, WB, ELISA. CEACAM8 (human), mAb (GM2H6) ALX-805-088-C100 100 µg CD5L (mouse), mAb (1F1G5i) CLONE: GM2H6. ISOTYPE : Mouse IgG1. IMMUNOGEN : Vector containing the ALX-803-338-C100 100 µg cDNA of human CEACAM8. SPECIFICITY: Recognizes human CEACAM8. Does CLONE: 1F1G5i. ISOTYPE: Rat IgG. IMMUNOGEN: Recombinant mouse CD5L. not cross-react with human CEACAM1, 3, 4, 5, 6, 7, or PSG1. APPLICATION : SPECIFICITY: Recognizes mouse CD5L. APPLICATION: IP, WB, ELISA. FC, ELISA. CEACAM19 (human), mAb (HY-8H10) ALX-805-089-C100 100 µg BAFF CLONE: HY-8H10. ISOTYPE : Mouse IgG1. IMMUNOGEN : Vector containing the cDNA of human CEACAM19. SPECIFICITY : Recognizes human CEACAM19. BAFF (BLyS; TALL1) is a cytokine expressed predomi- Does not cross-react with human CEACAM1, 3, 4, 5, 6, 7, 8, 20, or 21. AP- nantly by cells of the immune system such as neu- PLICATION : FC, ELISA. trophils, monocytes, macrophages, dendritic cells, follicular dendritic cells, activated T cells and some malignant B cells. BAFF is a master regulator of periph- eral B cell survival, and also acts in processes such as immunoglobulin isotype switch and B cell co-stimula- tion. Besides its major role in B cell biology, BAFF co- New Antibodies stimulates activated T cells. In humans, elevated levels of soluble BAFF have been detected in the serum of patients with various autoimmune diseases. FIGURE: Spectral confocal microscopy of CHO cells using CEACAM19 (human), mAb BAFF-R (human), mAb (HuBR9.1) (HY-8H10) (Prod. No. ALX-805-089). CHO cells were transiently transfected with ALX-804-883-C100 100 µg an expression vector encoding CEACAM19. Binding of CEACAM19 (human), mAb (HY-8H10) was visualized with a FITC-conjugated secondary antibody (green). Actin CLONE: HuBR9.1. ISOTYPE: Mouse IgG1. IMMUNOGEN: Cells transfected filaments are labeled with Alexa Fluor-555 Phalloidin (red). Cell nuclei are stained with human BAFF-R. SPECIFICITY: Recognizes human BAFF-R. with DAPI (blue). APPLICATION: FC. BAFF (human), mAb (blocking) (4.62) CEACAM20 (human), mAb (HT-12D8) ALX-804-882-C100 100 µg ALX-805-090-C100 100 µg CLONE: 4.62. ISOTYPE: Rat IgG2. IMMUNOGEN: HA-tagged human BAFF. CLONE: HT-12D8. ISOTYPE : Mouse IgG1. IMMUNOGEN : Vector containing the SPECIFICITY: Recognizes human BAFF. APPLICATION: ELISA. cDNA of human CEACAM20. SPECIFICITY : Recognizes human CEACAM20. Does not cross-react with human CEACAM1, 3, 4, 5, 6, 7, 8, 19, or 21. AP- BAFF (human), mAb (2.81) PLICATION : FC, ICC, ELISA. ALX-804-884-C100 100 µg PSG1 (human), mAb (BAP3) CLONE: 2.81. ISOTYPE: Rat IgG2. IMMUNOGEN: HA-tagged human BAFF. SPECIFICITY: Recognizes human BAFF. APPLICATION: ELISA. ALX-805-087-C100 100 µg CLONE: BAP3. ISOTYPE : Mouse IgG1. IMMUNOGEN : Extracted human PSG1. SPECIFICITY : Recognizes an epitope in the B2 domain of human PSG1. Does New available: not cross-react with CEACAM1, 3, 5, 7 or 8. APPLICATION : FC. BAFF (soluble) (human), matched pair detection set AG-46B-0001-001 1 Set www.enzolifesciences.com
  9. 9. 9 LC3 Microtubule-associated protein 1 light chain 3 (LC3) belongs to the family of autophagy-defective gene-8 (Atg-8)-related LC3B, mAb (5F10) proteins. It is expressed at sufficient high levels and efficient- ALX-803-080-C100 100 µg ly recruited to autophagic vesicles in cells and tissues. CLONE: 5F10. ISOTYPE: Mouse IgG1. IMMUNOGEN: Synthetic peptide corre- sponding to the N-terminus of LC3B. SPECIFICITY: Recognizes human, mouse, LC3B, mAb (2G6) rat, dog and hamster LC3B. Recognizes both forms of endogenous LC3B. Detects a band of ~18kDa (LC3B-I; cytoplasmic form) and a band of ~16kDa ALX-803-081-C100 100 µg (LC3B-II; lipidated form) by Western blot. APPLICATION: IHC, WB. CLONE: 2G6. ISOTYPE: Mouse IgG1. IMMUNOGEN: Synthetic peptide corre- sponding to the N-terminus of LC3B. SPECIFICITY: Recognizes human, mouse, unstimulated +vinblastine rat, monkey and hamster LC3B. Recognizes both forms of endogenous LC3B. Detects a band of ~18kDa (LC3B-I; cytoplasmic form) and a band of ~16kDa (LC3B-II; lipidated form) by Western blot. APPLICATION: IHC, WB. LC3, mAb (5H3) FIGURE: Endogenous LC3 punctae detected using LC3B, mAb (5F10) ALX-803-082-C100 100 µg (Prod. No. ALX-803-080) CLONE: 5H3. ISOTYPE: Mouse IgG1. IMMUNOGEN: Synthetic peptide corre- METHOD: The majority of LC3 was diffusely localized in unstimulated COS-7 cells, sponding to an internal sequence identical in LC3A, LC3B and LC3C. SPE- wheres punctated signals of LC3 increase after induction of autophagy by vinblastin CIFICITY: Recognizes human LC3. Recognizes both forms of endogenous LC3. stimulation for 2h. Cells were fi xed with paraformaldehyde followed by methanol treat- ment. Cells were permeabilized with 0.3% Triton X-100. (Image courtesy of I. Ciechom- Detects a band of ~18kDa (LC3-I; cytoplasmic form) and a band of ~16kDa ska and A. Tolkovsky, University of Cambridge, UK.) (LC3-II; lipidated form) by Western blot. APPLICATION: IHC, WB. CRISP3 Cysteine-rich secretory protein 3 (CRISP3) belongs to the cysteine-rich secretory protein family. It is up-regulated in CRISP3 (human), mAb (LV-2A2) malignant prostatic epithelium and can therefore be used as ALX-805-093-C100 100 µg a potential prostate cancer biomarker. CLONE: LV-2A2. ISOTYPE: Mouse IgG1. IMMUNOGEN: Vector containing the cDNA of human CRISP3. SPECIFICITY: Recognizes human CRISP3. APPLI- CATION: FC, ELISA. New Antibody Sample Packs The antibody sample packs include a set of related antibodies and positive control(s) for molecular chaperone, heat New Antibodies shock, oxidative stress, GPCR (G protein-coupled receptor), pain, obesity and cardiovascular research areas. They are designed to be cost effective and help you choose which of our many antibodies might work best for your particular sample type or application. Product Application Prod. No. Size HSP90, Ab sample pack WB ADI-PAK-010 8 x 25 µg HSP90, Ab sample pack with protein standards WB ADI-PAK-011 10 x 25 µg HSP70, Ab sample pack WB ADI-PAK-020 8 x 25 µg HSP70, Ab sample pack with protein standards WB ADI-PAK-021 10 x 25 µg HSP70, mAb sample pack WB ADI-PAK-040 8 x 25 µg HSP70, mAb sample pack with protein standards WB ADI-PAK-041 10 x 25 µg Heme oxygenase, Ab sample pack WB ADI-PAK-030 8 x 25 µg Heme oxygenase, Ab sample pack with protein standards WB ADI-PAK-031 10 x 25 µg GPCR pain, Ab sample pack Varies by product ADI-PAK-110 5 x 25 µg (Membrane ELISA, IHC, WB) GPCR obesity, Ab sample pack Varies by product ADI-PAK-120 6 x 25 µg (Membrane ELISA, IHC, WB) GPCR cardio, Ab sample pack Varies by product ADI-PAK-130 13 x 25 µg (Membrane ELISA, IHC, WB) Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation; IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide International Edition
  10. 10. 10 CD40/CD40L [CD154] CD40 is a costimulatory protein found on antigen presenting cells and is required for their activation. The binding of CD40L (CD154) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects. These include a variety of immune and inflammatory responses including stimulation of B cell proliferation, memory B cell development, T cell-dependent immunoglobulin class switching and induction of cytokine production. CD40L (soluble) (human), (rec.) Technical Note ALX-522-015-2010 2 x 10 µg MegaCD40L™ is a high activity construct in which ALX-522-015-6010 SuperPack 6 x 10 µg two trimeric CD40 ligands are artificially linked via the Produced in E. coli. The extracellular domain of human CD40L (CD154) collagen domain of ACRP30/adiponectin. This construct (aa 116-261) is fused at the N-terminus to a linker peptide (6 aa) and a very effectively simulates the natural membrane- FLAG®-tag. BIOLOGICAL ACTIVITY: Stimulates growth of B cells. The activity assisted aggregation of CD40L. It provides a simple and of rhsCD40L increases 1’000-fold (stimulation in the ng/ml range) in the equally potent alternative to mouse CD40L & enhancer presence of cross-linking enhancer (see Set Prod. No. ALX-850-064). For combinations (Prod. No. ALX-850-075). stimulation of mouse cells via CD40 use CD40L (soluble) (mouse), (rec.) (Prod. No. ALX-522-070 or ALX-850-075). LIT: Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with downregu- lation of its proapoptotic activity and loss of liver toxicity: P. Schneider, et al.; J. Exp. Med. 187, 12051 (1998)  Synergy between CD40 ligation and IL-4 on fibroblast proliferation involves IL-4 receptor sig- naling: S.P. Atamas, et al.; J. Immunol. 168, 1139 (2002)  Pro-inflammatory effect of TWEAK/Fn14 ACRP interaction on human umbilical vein endothelial cells: N. Harada, et al.; BBRC 299, 488 (2002)  HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection: S. Swingler, et al.; Nature 424, 213 (2003)  For a comprehensive bibliography please visit our website. CD40L (soluble) (human), (rec.) set CD40L ALX-850-064-KI01 1 Set Produced in E. coli. The extracellular domain of human CD40L (CD154) (aa 116-261) is fused at the N-terminus to a linker peptide (6 aa) and a FLAG®- tag. APPLICATION: Can be used to activate human B cells and dendritic cells. FIGURE: Graphical representation of MegaCD40L™ (soluble) (mouse), (rec.) Stimulates growth of human B cells. For stimulation of mouse cells via CD40 (Prod. No. ALX-522-120). use CD40 (mouse), mAb (FGK45) (Prod. No. ALX-805-046). SET CONTAINS: 100 • 10 µg of CD40L, Soluble (human) (rec.) (Prod. No. ALX-522-015) 90 MegaCD40L • 2 x 50 µg of Enhancer for Ligands (Prod. No. ALX-804-034), which in- 80 rhsCD40L rhsCD40L + enhancer creases the biological activity of rhsCD40L at least 1’000-fold. 70 CD40/CD40L [CD154] LIT: Conversion of membrane-bound Fas(CD95) ligand to its soluble form is associated with down- 60 regulation of its proapoptotic activity and loss of liver toxicity: P. Schneider, et al.; J. Exp. Med. 187, 1205 (1998)  CD40 induces apoptosis in carcinoma cells through activation of cytotoxic ligands of 50 the tumor necrosis factor superfamily: A.G. Eliopoulos, et al.; Mol. Cell. Biol. 20, 5503 (2000)  TNF 40 receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages: L. Mukundan, et al.; J. Immunol. 174, 1018 (2005)  Enhanced ac- 30 tivation of human dendritic cells by inducible CD40 and Toll-like receptor-4 ligation: N. Lapteva, et al.; Cancer Res. 67, 10528 (2007)  For a comprehensive bibliography please visit our website. 20 37 46 15 05 02 00 37 12 3 1 4 0 33 11 1. 0. 0. 0. 0. 10 MegaCD40L™ (soluble) (human), (rec.) ng/ml ALX-522-110-C010 10 µg FIGURE: MegaCD40L (soluble) (human), (rec.) (Prod. No. ALX-522-110) does not need an enhancer to induce B cells activation. Produced in CHO cells. The extracellular domain of human CD40L METHOD: PBL cells were incubated in 96-well plates (2x105 cells/well in 100µl (CD154) (aa 116-261) is fused at the N-terminus to mouse ACRP30head- RPMI supplemented with 10% FCS) for 24 hours at 37°C with the indicated less (aa 18-111) and a FLAG®-tag. BIOLOGICAL ACTIVITY: Binds to human concentration of MegaCD40L (soluble) (human), (rec.) or CD40L (soluble) (hu- CD40. Induces B cell activation (as demonstrated by dose-dependent man), (rec.) (Prod. No. ALX-522-015) in the presence and absence of 1µg/ml upregulation of CD86). enhancer (Prod. No. ALX-804-034). Cells were washed with PBS and stained LIT: Two adjacent trimeric Fas ligands are required for Fas signaling and formation of a death- with 2µl each CD86-PE and CD19-FITC in 50µl FACS buffer (PBS, 5% fetal calf inducing signaling complex: N. Holler, et al.; Mol. Cell. Biol. 23, 1428 (2003)  Impaired CD40L serum, 0.02% azide) for 20 min. at 4°C in the dark. After two washes in FACS signaling is a cause of defective IL-12 and TNF-alpha production in Sezary syndrome: circum- buffer, samples were then analyzed by flow cytometry. vention by hexameric soluble CD40L: L.E. French, et al.; Blood 105, 219 (2005) Related Products: Product Prod. No. Size CD40 (human):Fc (human), (rec.) ALX-522-016-C050 50 µg CD40 (human):COMP (human), (rec.) ALX-522-064-C010 10 µg CD40L (soluble) (mouse), (rec.) ALX-522-070-2010 2 x 10 µg CD40L (soluble) (mouse), (rec.) set ALX-850-075-KI01 1 Set MegaCD40L™ (soluble) (mouse), (rec.) ALX-522-120-C010 10 µg Fc (human):CD40L (soluble) (human), (rec.) ALX-522-076-C010 10 µg Fc (human):CD40L (soluble) (mouse), (rec.) ALX-522-072-C010 10 µg www.enzolifesciences.com
  11. 11. 11 Cytokine Kits – Cancer and Immunology Cytokine research has led to a better understanding of cancer biology. Inappropriately dividing cells activate immune responses first modulated by macrophages that secrete cytokines to stimulate dendritic cells to mature and present antigens to T cells. Ideally these T cells destroy the tumor. Tumor cells may avoid destruction by producing molecules that interfere with antigen presentation or maturation of dendritic cells. The inflammatory response may even aid in the growth of the tumor by promoting angiogenesis. Targeting these molecules for novel cancer therapeutics will aid in the treatment of many solid tumors and improve patient outcomes. Product Application Sensitivity Prod. No. Size IFN-g (human), EIA kit Culture supernatants, plasma, serum, and 2 pg/ml ADI-900-136 1 x 96 wells urine (range 25.6 - 1,000 pg/ml) IFN-g (mouse), EIA kit Culture supernatants, plasma, serum, and 10 pg/ml ADI-900-137 1 x 96 wells urine (range 37 - 3,000 pg/ml) IL-1β (human), EIA kit Plasma, serum, and urine of human origin 1 pg/ml ADI-900-130 1 x 96 wells (range 10.24 - 400 pg/ml) IL-1β (mouse), EIA kit Culture supernatants, plasma, and serum 3 pg/ml ADI-900-132 1 x 96 wells of mouse origin (range 15.6 - 1,000 pg/ml) IL-1β (rat), EIA kit Culture supernatants, plasma, and serum 12 pg/ml ADI-900-131 1 x 96 wells of rat origin (range 25.6 - 2,500 pg/ml) Cytokine Kits – Cancer and Immunology IL-2 (human), EIA kit Culture supernatants, plasma, and serum 6.6 pg/ml ADI-900-118A 1 x 96 wells (range 7.81 - 500 pg/ml) IL-2 (mouse), EIA kit Culture supernatants and serum 3.12 pg/ml ADI-900-042 1 x 96 wells (range 7.81 - 1,000 pg/ml) IL-4 (human), EIA kit Culture supernatants, plasma, serum, and 2 pg/ml ADI-900-145 1 x 96 wells urine (range 10.24 - 400 pg/ml) IL-4 (mouse), EIA kit Culture supernatants and serum 4.34 pg/ml ADI-900-043 1 x 96 wells (range 7.81 - 1,000 pg/ml) IL-6 (human), EIA kit Culture supernatants, plasma, serum, and 6.01 pg/ml ADI-900-033 1 x 96 wells urine (range 7.81 - 500 pg/ml) IL-6 (mouse), EIA kit Culture supernatants and serum 1.01 pg/ml ADI-900-045 1 x 96 wells (range 7.81-1,000 pg/ml) IL-8 (human), EIA kit Culture supernatants, plasma, and serum 0.64 pg/ml ADI-900-156 1 x 96 wells (range 7.8-1,000 pg/ml) IL-10 (human), EIA kit Culture supernatants, plasma, and serum 3.75 pg/ml ADI-900-036 1 x 96 wells (range 7.81 - 500 pg/ml) IL-10 (mouse), EIA kit Culture supernatants and serum 12 pg/ml ADI-900-148 1 x 96 wells (range 37 - 3,000 pg/ml) IL-33 (soluble) (human), Biological fluids (serum and cell culture 5 pg/ml APO-54N-025-KI01 5 x 96 wells detection set supernatant) (range 0 - 500 pg/ml) [for ELISA application] Osteoprotegerin Serum, plasma and urine 2.8 pg/ml ALX-850-280-KI01 1 x 96 wells (human), ELISA kit Free Osteoprotegerin Cell culture supernatant, plasma and 2 pg/ml APO-54N-028-KI01 5 x 96 wells (human), detection set serum (range 0 to 250 pg/ml) [for ELISA application] Free Osteoprotegerin Biological fluids (serum, plasma and 20 pg/ml APO-54N-042-KI01 1 x 96 wells (human), ELISA kit cell culture supernatant) (range 0.031 to 2 ng/ml) TGF-β1 EIA kit Culture supernatants, plasma, and serum 3.3 pg/ml ADI-900-155 1 x 96 wells of human, mouse, rat, and cow origin (range 31.25 - 1000 pg/ml) TNF-a (human), EIA kit Culture supernatants, plasma, and serum 8.43 pg/ml ADI-900-099 1 x 96 wells (range 15.63 - 1,000 pg/ml) TNF-a (mouse), EIA kit Culture supernatants and serum 3.9 pg/ml ADI-900-047 1 x 96 wells (range 31.25 - 2,000 pg/ml) TNF-a (rat), EIA kit Culture supernatants 12.0 pg/ml ADI-900-086A 1 x 96 wells (range 31.3 - 2000 pg/ml) TNF-a, soluble (human), ALX-850-060-KI01 1 Set (rec.) set TNF-a, soluble (mouse), ALX-850-061-KI01 1 Set (rec.) set Purified (PF) = Purified (Preservative free); FC = Flow Cytometry; ICC = Immunocytochemistry; IP = Immunoprecipitation; IHC = Immunohistochemistry (FS = Frozen Sections, PS = Paraffin Sections); WB = Western blot; BP = Blocking Peptide International Edition
  12. 12. Wnt Signaling in Cancer North/South America ENZO LIFE SCIENCES INTERNATIONAL, INC. 5120 Butler Pike Plymouth Meeting, PA 19462-1202 / USA The Wnt signaling pathway is a complex network Tel. 1-800-942-0430 / (610) 941-0430 of proteins including β-catenin, Wnt, frizzled and Fax (610) 941-9252 LRP receptors, dishevelled, GSK-3, APC, TCF, axin, info-usa@enzolifesciences.com and others. When Wnt binds to frizzled, dishevelled is recruited to the membrane and GSK-3 (which Switzerland & Rest of Europe normally phophorylates β-catenin) is inhibited by ENZO LIFE SCIENCES AG this activation. This inhibition of GSK-3 permits Industriestrasse 17, Postfach β-catenin to become stabilized and releases it from CH-4415 Lausen / Switzerland the axin complex. β-Catenin then accumulates Tel. + 41/0 61 926 89 89 in the cytosol, translocates to the nucleus, and Fax + 41/0 61 926 89 79 forms a complex with TCF to eventually regulate info-ch@enzolifesciences.com cellular proliferation (e.g. osteoblast and neuronal development), survival and apoptosis through the Benelux induction of target nuclear genes. ENZO LIFE SCIENCES BVBA Melkerijweg 3 Several components (e.g. APC, axin, TCF) of the BE-2240 Zandhoven / Belgium Wnt signaling pathway have been implicated in Tel. +32/0 3 466 04 20 human tumors or experimental cancer models. Fax +32/0 3 466 04 29 In multiple myeloma, Dkk-1 is overexpressed info-be@enzolifesciences.com and facilitates increased bone resorption and the appearance of osteolytic lesions characteristic of France this type of cancer. Dkk-1 inhibits the Wnt pathway ENZO LIFE SCIENCES FRANCE (see image) by binding to the LRP5/6 co-receptors, c/o Covalab s.a.s preventing interaction with Wnt, and facilitating the 13, avenue Albert Einstein, degradation of β-catenin through phosphorylation 69100 Villeurbanne / France by GSK-3. Tel. +33/0 472 440 655 Fax +33/0 437 484 239 info-fr@enzolifesciences.com Dkk-1 (human), EIA kit Dkk-1 (rat), EIA kit ADI-900-151 1 x 96 wells ADI-900-171 1 x 96 wells Germany For the quantitative determination of human Dkk-1 in culture For the quantitative determination of rat Dkk-1 in culture ENZO LIFE SCIENCES GmbH supernatants, plasma, and serum. SENSITIVITY: 0.98 pg/ml supernatants, plasma, and serum. SENSITIVITY: 26.1 pg/ml Marie-Curie-Strasse 8 (range 7.81-500 pg/ml). (range 39.1 - 1250 pg/ml). DE-79539 Lörrach / Germany Tel. +49/0 7621 5500 526 Dkk-1 (mouse), EIA kit NEW Toll Free: 0800 6649518 ADI-900-172 1 x 96 wells Fax +49/0 7621 5500 527 For the quantitative determination of mouse Dkk-1 in culture info-de@enzolifesciences.com supernatants, plasma, and serum. SENSITIVITY: 116.7 pg/ml (range 125 - 4,000 pg/ml). UK & Ireland ENZO LIFE SCIENCES (UK) LTD. Dkk-1 (mouse), (rec.) NEW Palatine House ADI-KPR-CP100-D 50 µg Matford Court Exeter EX2 8NL / UK ADI-KPR-CP100-F 200 µg Tel. 0845 601 1488 (UK customers) - Mature recombinant mouse Dkk-1 protein with N-terminal Tel. +44/0 1392 825900 (overseas) His-tag, expressed in E. coli. Fax +44/0 1392 825910 info-uk@enzolifesciences.com For Local Distributors please visit our Website. www.enzolifesciences.com ZZ-T0310-1002

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