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Signal Transduction Discover Signal Transduction Discover. Optimize. Verify. Optimize > ELISAs Discover > Antibody Arrays > Small Molecule Libraries Verify > Antibodies Verify > Antibodies Quick Guide Discover Proteome Profiler™ Antibody Arrays ................................3 Tocriscreen™ Collections ........................................4 Optimize R&D Systems® ELISA Kits and Development Systems ..............5–7 Verify Novus Biologicals® and R&D Systems® Antibodies .................8–9 Product Listings Simple Western™ Antibodies .................................10–11 Proteome Profiler™ Antibody Arrays ............................12–14 Tocris® Small Molecules .......................................15 2 Discover What You Might Be Missing Unexpected, interesting results can be missed when only a subset of proteins within a given family or signaling pathway is analyzed using standard Western blots. Proteome Profiler™ Antibody Arrays allow you to analyze the expression levels or phosphorylation status of many proteins simultaneously, an approach that could increase your chances of discovering a novel pathway or cellular response. Proteome Profiler™ Antibody Arrays Proteome Profiler membrane-based antibody A. arrays consist of capture antibodies specific ERK1/2 (T202/Y204, T185/Y187) Akt (S473) STAT3 (S727) c-Jun (S63) for up to 119 analytes spotted in duplicate on a nitrocellulose membrane. Each array is EGF R (Y1086) designed to analyze a particular protein family CREB (S133) or cellular process. Comprehensive in scope, the data generated from each of these arrays can uncover unexpected cellular responses, Untreated PD 98059, EGF such as crosstalk between signaling pathways or off-target pharmacological effects. The arrays also eliminate the time-consuming steps of gel electrophoresis and protein transfer that are necessary when performing EGF SL 327, EGF a Western blot. In addition, the arrays require no specialized equipment. If you can collect data from a Western blot, you have the equipment to run a membrane-based array experiment. PD 0325901, EGF U0126, EGF Features B. • Hundreds of citations in primary literature ) 35 3 Untreated PD 98059 • Ideal for visualizing signaling crosstalk 30 EGF SL 327 PD 0325901 U0126 • Easier to perform than a Western blot 25 • Hands-on time of 3 hours 20 15 Assay Principle 10 Light 5 Substrate Phosphorylation (Pixel Density x10 0 ERK1/2 Akt (S473) STAT3 (S727) c-Jun (S63) StreptavidinHRP Biotin (T202/Y204, T185/Y187) Detection Antibody Induction and Inhibition of Kinase Phosphorylation in T47D Cells. The T47D human breast cancer cell line was untreated, treated with 100 ng/mL Recombinant Human EGF (R&D Systems; Catalog # 236-EG) for 15 minutes, or EGF following a 2 hour pretreatment with the MEK inhibitors PD 0325901 (10 µM; Tocris; Catalog # 4192), PD 98059 (20 µM; Tocris; Catalog #1213), SL 327 (10 µM; Tocris; Catalog # 1969), or U0126 (10 µM; Tocris; Catalog # 1144). The phosphorylation status was Target Analyte determined using the Proteome Profiler Human Phospho-Kinase Array (R&D Systems; Catalog # ARY003B). Membranes were exposed to X-ray film (A) and histograms were generated from pixel density measurements (B). Capture Antibody Array Membrane Membrane-based Antibody Array Assay Principle. Antibodies immobilized on nitrocellulose membranes are used to capture specific proteins from cell lysates. Target proteins are detected using a cocktail of biotinylated detection antibodies and Streptavidin-HRP, or an HRP- conjugated pan anti-Phospho-Tyrosine antibody. Bound analytes are visualized with chemiluminescence. 3 Learn more | rndsystems.com/proteomeprofiler Discover What You Might Be Missing Tocriscreen™ Tocriscreen collections are unique small molecule libraries, designed for screening based on chemical genetics, chemical biology, Featured Collections receptor de-orphaning, target validation, or drug re-profiling. Comprised of biologically active compounds selected from the Tocris Tocriscreen Total (Tocris; Catalog # 2884) catalog, Tocriscreen collections provide wide 1120 biologically active compounds pre-dissolved in DMSO (250 μL 10 mM solutions) coverage of the most important targets covered in biochemical and cellular screening Includes compounds targeting 5-HT, glutamate, acetylcholine, and adrenergic receptors; assays. Used in both high-throughput and high inhibitors of PDE, PKC, and ROCK; and a number of ion channel blockers. content screening, Tocriscreen collections Tocriscreen Mini (Tocris; Catalog # 2890) provide an indispensable starting point for 1120 biologically active compounds pre-dissolved in DMSO (50 μL 10 mM solutions) modern drug discovery. The same high quality compounds as the Tocriscreen Total, in smaller volumes. The libraries are available pre-dissolved in Tocriscreen Kinase Inhibitor Toolbox (Tocris; Catalog # 3514) DMSO, and include compounds targeting 80 Kinase inhibitors supplied pre-dissolved in DMSO (250 μL 10 mM solutions) GPCRs, kinases, ion channels, nuclear Includes the kinase inhibitors U0126 (Catalog # 1144) and PD 98059 (Catalog # 1213). receptors, transporters and stem cell biology. Many of the compounds are unavailable Tocriscreen Stem Cell Toolbox (Tocris; Catalog # 5060) elsewhere. 80 stem cell modulators supplied pre-dissolved in DMSO (250 μL 10 mM solutions) Includes the stem cell compounds DAPT (Catalog # 2634), Y-27632 (Catalog # 1254), Features SB 431542 (Catalog # 1614) and CHIR 99021 (Catalog # 4423). • All compounds are biologically active Tocriscreen Epigenetics Toolbox (Tocris; Catalog # 5268) New • Full chemical and biological data available 80 epigenetic modulators supplied pre-dissolved in DMSO (250 μL 10 mM solutions) • Many compounds are unique to Tocris Includes the epigenetics compounds (+)-JQ1 (Catalog # 4499), A 366 (Catalog # 5163) and • Exceptional purity JIB 04 (Catalog # 4972). • Guaranteed resupply of compounds Citations 1. Beacham, D.W. et al. (2010) Cell-based potassium ion channel screening using the FluxORTM assay. J. Biomol. Screen. 15:441-6. 2. Hattori, H. et al. (2010) Small-molecule screen identifies reactive oxygen species as key regulators of neutrophil chemotaxis. Proc. Natl. Acad. Sci. USA 107:3546-51. 3. Li, Y. et al. (2011) Generation of iPSCs from mouse fibroblasts with a single gene, Oct4, and small molecules. Cell Res. 21:196-204. 4. Jester, B.W. et al. (2010) A coiled-coil enabled split-luciferase three-hybrid system: applied toward profiling inhibitors of protein kinases. J. Am. Chem. Soc.132 :11727-35. 5. Moujalled, D. et al. (2013) Kinase inhibitor screening identifies cyclin-dependent kinases and glycogen synthase kinase 3 as potential modulators of TDP-43 cytosolic accumulation during cell stress. PLoS One 8:e67433. 6. Edwards, B.S. et al. (2014) The University of New Mexico Center for Molecular Discovery. Comb. Chem. High Throughput Screen. 17:256-65. 4 Learn more | tocris.com/screeninglibraries Optimize Experimental Conditions Faster with ELISAs The Surveyor™ IC (Intracellular) ELISA Kits, DuoSet® IC ELISA Development Systems, and Cell-Based ELISA Kits each provide as much data as do approximately eight individual Western blots. More important, the data obtained from our ELISA assays exhibit excellent correlation with results from Western blots performed in parallel. These ELISA-based formats provide a more efficient way to optimize your experimental conditions and clarify the best way forward. DuoSet® IC ELISA Development Systems DuoSet IC ELISA Development Systems offer EGF + PD 0325901 Untreated EGF 50 nM 5 nM 1 nM 250 pM an economical alternative to complete A. Surveyor IC ELISA Kits. They contain the Phospho- components required for developing an assay, ERK1/ERK2 including capture and detection antibodies, protein standard or control, and Streptavidin- HRP. Each DuoSet IC ELISA Development Total ERK1/ERK2 System undergoes an extensive validation process to ensure specificity, minimizing the time required to perform a successful assay. Features B. 2.0 • High sensitivity – requires small sample volume • Economical (O.D.) 1.5 • Flexible format • Quantitative without image software analysis 1.0 ERK1/ERK2 • Adaptable to high-throughput applications 0.5 Phospho- 0 Untreated EGF 50 nM 5 nM 1 nM 250 pM EGF + PD 0325901 Quantification of Phospho-ERK1/ERK2 in T47D Cells.The T47D human breast cancer cell line was treated with the indicated concentrations of PD 0325901 (Tocris; Catalog # 4192) for 2 hours, followed by treatment with 100 ng/mL Recombinant Human EGF (R&D Systems; Catalog # 236-EG) for 5 minutes. The levels of phospho-ERK1 (T202/Y204)/ERK2 (T185/Y187) were detected by Western blot (A) and quantified using the Phospho-ERK1 (T202/Y204)/ERK2 (T185/Y187) DuoSet IC ELISA Development System (R&D Systems; Catalog # DYC1018B) (B). 5 Learn more | rndsystems.com/duoseticphospho and rndsystems.com/duosetictotal Optimize Experimental Conditions Faster with ELISAs Surveyor™ IC ELISA Kits Complete kits using a 96-well microplate format, Surveyor IC ELISAs provide all the components M U0126 necessary for measuring the levels of total or M U0126 µ M U0126 µ phosphorylated proteins. Protein levels are µ A. Untreated PDGF PDGF + 1 PDGF + 10 PDGF + 100 easily quantified using the calibrated standard included in each kit, and the sensitivity of the assay permits the use of small sample volumes. Phospho- ERK1/ERK2 Features • Fully validated, complete kits • High sensitivity – requires small sample volume Total ERK1/ERK2 • Quantitative without image software analysis • Adaptable to high-throughput applications Assay Principle B.
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