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PRODUCT DESCRIPTION Protein Kinase and Protein Tyrosine Kinase Inhibitors WORKING CONCENTRATION QUANTITY CATALOG CODE 2-Aminopurine PKR inhibitor 1 - 10 mM 250 mg tlrl-apr p 157 AG490 JAK family tyrosine kinase inhibitor 1 -100 μM 10 mg tlrl-ag4 p 157 H-89 PKA inhibitor 5 - 50 μM 5 mg tlrl-h89 p 157 Epigenetic Inhibitors 5-Aza-cytidine DNA methyltransferase inhibitor 2 μM 100 mg inh-aza p 157 5-Aza-2’-deoxycytidine DNA methyltransferase inhibitor 0.1 - 10 μM 10 mg met-adc-1 p 157 Bix-01294 G9a histone methyltransferase inhibitor 1 μM 2 mg inh-bix p 157 Trichostatin A Histone deacetylase inhibitor 150 - 300 nM 1 mg met-tsa-1 p 157 Valproic Acid Histone deacetylase inhibitor 2 mM 5 g inh-vpa p 157 Heat Shock Protein Inhibitors Geldanamycin (GA) Hsp90 inhibitor 1 nM - 10 μM 5 mg ant-gl-5 p 158 17-AAG GA analogue 1 nM - 10 μM 5 mg ant-agl-5 p 158 17-DMAG GA analogue 1 nM - 10 μM 5 mg ant-dgl-5 p 158 17-AEP-GA GA analogue 1 nM - 10 μM 1 mg ant-egl-1 p 158 17-DMAP-GA GA analogue 1 nM - 10 μM 1 mg ant-mgl-1 p 158 17-GMB-APA-GA GA analogue for conjugation to MAb 1 nM - 10 μM 1 mg gmbapa-ga p 158 17-NHS-ALA-GA GA analogue 1 nM - 10 μM 1 mg ant-nhgl-1 p 158 Biotin-GA Biotin-labeled GA analogue 1 nM - 10 μM 1 mg ant-bgl-1 p 159 17-AAGH2 GA analogue 1 nM - 10 μM 1 mg ant-agh-1 p 159 17-DMAGH2 GA analogue 1 nM - 10 μM 1 mg ant-dgh-1 p 159 DNA Synthesis Inhibitors 5-Fluorocytosine DNA synthesis inhibitor 200 - 500 μg/ml 250 mg sud-5fc p 159 5-Fluorouracil DNA synthesis inhibitor 1 - 300 μg/ml 250 mg sud-5fu p 159 Ganciclovir DNA synthesis inhibitor 1 - 100 μg/ml 250 mg sud-gcv p 159 Contents and Storage Products are provided as solids and shipped at room temperature. Store at room temperature, 4°C or -20°C according to the product label. Geldanamycin and analogues, and triptolide should be kept in the dark. Products are stable at least 6 months. INFO www.invivogen.com/inhibitors 153 INHIBITORS 8
INHIBITORS 8 Pattern Recognition Receptor (PRR) Signaling Inhibitors BX795 - TBK/IKKε Inhibitor BX795, an aminopyrimidine compound, was developed as an inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1) 1 . It was recently shown to be a potent inhibitor of the IKK-related kinases, TANK-binding kinase 1 (TBK1) and IKKε, and hence of IRF3 activation and IFN-β production 2 . BX795 inhibits the catalytic activity of TBK1/IKKε by blocking their phosphorylation. Chloroquine - Inhibitor of Endosomal Acidification Chloroquine is a lysosomotropic agent that prevents endosomal acidification 3 . It accumulates inside the acidic parts of the cell, including endosomes and lysosomes. This accumulation leads to inhibition of lysosomal enzymes that require an acidic pH, and prevents fusion of endosomes and lysosomes. Chloroquine is commonly used to study the role of endosomal acidification in cellular processes, such as the signaling of intracellular TLRs 4, 5 . CLI-095 - TLR4 Signaling Inhibitor CLI095, also known as TAK-242, is a novel cyclohexene derivative that specifically suppresses TLR4 signaling, inhibiting the production of NO and proinflammatory cytokines 6 . It acts by blocking the signaling mediated by the intracellular domain of TLR4, but not the extracellular domain. It potently suppresses both ligand-dependent and -independent signaling of TLR4 7 . Cyclosporin A - Calcineurin inhibitor NEW Cyclopsporin A is a calcineurin inhibitor that exerts its immunosuppressive effects through the down-regulation of NFAT (nuclear factor of activated T cells) transcription factor, thus preventing the transcription of T cell effector cytokines 8 . Moreover, NFAT has been implicated in the downstream signaling of Dectin-1 which is important in the innate immune response against fungal infection 9 . Conversely, it has been demonstrated that inhibition of calcineurin in macrophages enhances NF-κB activation 10 and can trigger TLR signaling by activating both the MyD88-dependent and the MyD88-independent pathways 11 . Gefitinib - RIP2 Tyrosine Kinase inhibitor NEW Gefitinib (also known as Iressa) is a selective inhibitor of epidermal growth factor, a growth factor that plays a pivotal role in the control of cell growth, apoptosis, and angiogenesis. Recent studies demonstrated that Gefitinib can inhibit NOD2-induced cytokine release and NF-kB activation by inhibiting RIP2 (receptor-interacting protein 2) tyrosine phosphylation which is critical for activation of NOD2 downsream signaling pathways 12 . Gefitinib is used in the treatment of advanced nonsmall cell lung cancer 13 . OxPAPC - TLR2 and TLR4 Inhibitor OxPAPC (1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine), is an oxidized phospholipid that has been shown to inhibit the signaling induced by bacterial lipopeptide and lipopolysaccharide (LPS). It acts by competing with CD14, LBP and MD2, the accessory proteins that interact with bacterial lipids, thus blocking the signaling of TLR2 and TLR4 14, 15 . Pepinh-MYD - MyD88 inhibitory peptide Pepinh-MYD is a 26 aa peptide that blocks MyD88 signaling by inhibiting its homodimerization through binding. Pepinh-MYD contains a sequence from the MyD88 TIR homodimerization domain (RDVLPGT) 16 preceeded by a protein transduction sequence (RQIKIWFQNRMKWKK) derived from antennapedia which enables the peptide to translocate through the cell membrane 17 . Pepinh-MYD is provided with a control peptide. Pepinh-TRIF - TRIF inhibitory peptide Pepinh-TRIF is a 30 aa peptide that blocks TRIF signaling by interfering with TLR-TRIF interaction. Pepinh-TRIF contains the 14 aa that correspond to the sequence of the BB loop of TRIF (FCEEFQVPGRGELH) 18 linked to the cell-penetrating segment of the antennapedia homoedomain (RQIKIWFQNRMKWKK) 17 . Pepinh-TRIF is provided with a control peptide. Polymyxin B - Inhibitor of LPS-induced TLR4 activation Polymyxin B (PMB) is a cyclic cationic polypeptide antibiotic produced by the soil bacterium Paenibacillus polymixa. PMB blocks the biological effects of Gram negative LPS (endotoxin) through binding to lipid A, the toxic component of LPS, which is negatively charged 19, 20 . The neutralizing effect of PMB on LPS is dose-related and specific for LPS 21 . PMB is widely used to eliminate the effects of endotoxin contamination, both in vitro and in vivo. Rapamycin - mTOR Inhibitor Rapamycin is an inhibitor of the Ser/Thr protein kinase named "mammalian target of rapamycin" (mTOR) that regulates cell growth and metabolism in response to environmental cues. mTOR is a downstream target of PI3K, an important actor in TLR signaling 22 . Rapamycin was shown to block TLR2- and TLR4-mediated expression of TNF-a and IL-6 in neutrophils stimulated with Pam3CSK4 or LPS 23 . Z-VAD-FMK - Caspase Inhibitor Z-VAD-FMK is a cell-permeable pan-caspase inhibitor that irreversibly binds to the catalytic site of caspase proteases 24 . The peptide is O-methylated in the P1 position on aspartic acid, providing enhanced stability and increased cell permeability. Z-VAD-FMK is used in apoptosis studies and also in inflammasome studies. It is a potent inhibitor of caspase-1 activation in NLRP3-induced cells 25 . 1. Feldman RI. et al., 2005. Novel Small Molecule Inhibitors of 3-Phosphoinositide-dependent Kinase-1. J. Biol. Chem., 280: 19867 - 19874. 2. Clark K. et al., 2009. Use of the Pharmacological Inhibitor BX795 to Study the Regulation and Physiological Roles of TBK1 and I{kappa}B Kinase {epsilon}: a distinct upstream kinase mediates Ser-172 phosphorylation and activation. J. Biol. Chem. 284: 14136 - 14146. 3. Steinman RM. et al., 1983. Endocytosis and the recycling of plasma membrane. J. Cell. Biol. 96:1-27. 4. Rutz, M. et al., 2004. Toll-like receptor 9 binds singlestranded CpG-DNA in a sequence- and pH-dependent manner. Eur. J. Immunol. 34:2541-2550. 5. Hart OM. et al., 2005.TLR7/8-Mediated Activation of Human NK Cells Results in Accessory Cell-Dependent IFN-{gamma} Production. J. Immunol., 175: 1636 - 1642. 6. Li M. et al., 2006. A Novel Cyclohexene Derivative, Ethyl (6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex- 1-ene-1-carboxylate (TAK-242), Selectively Inhibits Toll-Like Receptor 4-Mediated Cytokine Production through Suppression of Intracellular Signaling. Mol. Pharmacol., 69: 1288 - 1295. 7. Kawamoto T. et al., 2008. TAK-242 selectively suppresses Toll-like receptor 4-signaling mediated by the intracellular domain. Eur J Pharmacol. 584(1):40-8. 8. Chow CW. et al., 1999. Requirement for transcription factor NFAT in interleukin-2 expression. Mol Cell Biol. 19(3): 2300-07. 9. Goodridge et al. 2007. Dectin-1stimulation by Candida albicans yeast or zymosan 154 www.invivogen.com/inhibitors
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INNOVATION WITHIN REACH InvivoGen
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CONTENTS AT A GLANCE 1 CELL CULTURE
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4 CYTOKINE SIGNALING TABLE of CONTE
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Mycoplasma Detection & Elimination
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PlasmoTest Contents - HEK-Blue -2
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Primocin - The Antimicrobial Shiel
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SEAP Reporter Gene System Secreted
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HEK-Blue Detection - Real-Time Det
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Blasticidin S Description Blasticid
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LyoVec New formulation LyoVec is
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Poly-Arginine-HA Tagged Reprogrammi
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LENTI-Smart - Lentiviral Vector Pr
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Lentiviral Vector Production and Ce
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Antibody generation using pFUSE-CHI
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Engineering Fc regions for altered
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pBROAD & pWHERE - Optimized Vector
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pSELECT-Tag - Expression of a GFP-,
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pVIVO - Expression of Two Genes of
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pORF Description pORF plasmids feat
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Prom A-List - Human and Rodent Pro
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PROMOTER GENE TISSUE DISTRIBUTION S
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ChemiComp E. coli ChemiComp E. coli
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Fast-Media ® Preparation 1. Empty
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RIG-I-like Receptors 54 RLR & RLR-R
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Toll-Like Receptors Toll-Like Recep
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www.invivogen.com/innate-immunity 5
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IPAF and NAIP5 IPAF (NLRC4, CLAN/CA
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C-Type Lectin Receptors C-type lect
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pUNO pUNO-HA Toll-Like Receptors (T
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GENE NAME/ALIASES DESCRIPTION CAT.
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pDUO - Gene Associations Features a
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pZERO-TLR & pDeNy - Dominant Negati
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293/TLR & 293/NOD Clones 293/TLR Cl
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Response of HEK-Blue hTLR2 cells t
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Ramos-Blue Cells - NF-kB/AP-1 Repo
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MEF Cells C3H/TLR4mut & C3H/WT MEFs
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Antibodies for Detection ANTIBODY D
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- NF-kB binding site: Nuclear facto
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PRODUCT ORIGIN/DESCRIPTION TLR2 Ago
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PRODUCT ORIGIN/DESCRIPTION TLR9 Ago
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PRODUCT ORIGIN/DESCRIPTION Dectin-1
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LPS-PG (Porphyromonas gingivalis) R
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• FLA-ST ultrapure was purified b
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1. Zhao H. et al., 2004. Contributi
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1. Hornung V. et al., 2006. 5'-Trip
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TLR/NOD Ligand Screening InvivoGen
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Signal Transduction Inhibitors Invi
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Pepinh-MYD - MyD88 inhibitory pepti
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1. Martinon F,. et al., 2002. The i
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Nigericin - NLRP3 Inflammasome Indu
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Autophagy is a pathway by which cyt
Page 104 and 105: 4 CYTOKINE SIGNALING Cytokine Genes
Page 106 and 107: Blue Cytokine Reporter Cells Blue
Page 108 and 109: HEK-Blue IFN-a/b Cells - Human Typ
Page 110 and 111: HEK-Blue IL-6 Cells - IL6 Reporter
Page 112 and 113: HEK-Blue IL-1b Cells - IL-1b Repor
Page 114 and 115: HEK-Blue IL-33/IL-1b Cells - IL-33
Page 116 and 117: HEK-Blue CD40L Cells - CD40L Repor
Page 118 and 119: 5 ANTIBODIES & VACCINATION Antibodi
Page 120 and 121: Antibody generation using pFUSE-CHI
Page 122 and 123: Immunoglobulin A The mucosal surfac
Page 124 and 125: IgA Detection and Quantification In
Page 126 and 127: IgG Antibodies InvivoGen offers a s
Page 128 and 129: Mediators? 1. Leroux-Roels G., 2010
Page 130 and 131: Poly(I:C) Synthetic double-stranded
Page 132 and 133: pVAC - Induction of Neutralizing An
Page 134 and 135: CpG-Free DNA CpGs and the Immune Re
Page 136 and 137: pCpGfree-basic & pCpGfree-promoter
Page 138 and 139: pCpGfree-siRNA & pCpGfree-siRNADUO
Page 140 and 141: Custom-Made CpG-Free Genes InvivoGe
Page 143 and 144: RNA INTERFERENCE 7 psiRNA System I
Page 145 and 146: RNA INTERFERENCE 7 psiRNA-h7SK - 7S
Page 147 and 148: RNA INTERFERENCE 7 psiTEST System
Page 149 and 150: RNA INTERFERENCE 7 Ready-Made psiRN
Page 151 and 152: RNA INTERFERENCE 7 Custom-Made psiR
Page 153: INHIBITORS 8 Inhibitors PRODUCT DES
Page 157 and 158: INHIBITORS 8 Triptolide - NF-kB Inh
Page 159 and 160: INHIBITORS 8 Heat Shock Protein Inh
Page 161 and 162: 9 CUSTOM SERVICES TLR/NOD Ligand Sc
Page 163 and 164: CUSTOM SERVICES 9 Custom Cloning :
Page 165 and 166: CUSTOM SERVICES 9 Prices 164 TERMS
Page 167 and 168: 166 PRODUCT (QUANTITY) CAT. CODE PA
Page 173 and 174: A 17-AAG 17-AAGH2 17-AEP-GA 2-Amino
Page 175 and 176: - ODN 4084-F - ODN INH-1 - ODN INH-
Page 177 and 178: ARGENTINA Genbiotech S.R.L. Tel: +5
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