EMD Millipore—with the expertise of Calbiochem ® , Chemicon ® , and Upstate ® EMD Millipore is a division of Merck KGaA, Darmstadt, Germany Magna ChIP® HiSens Kits Excellent sensitivity from large or small chromatin amounts These kits combine a complete set of validated reagents with a detailed protocol to create a streamlined, high performance ChIP procedure that allows the use of the same kit for a variety of experimental conditions. Magna ChIP® HiSens Advantages • ChIP from a wide range of input amounts (10,000 to 1,000,000 cells) • Blended protein A/G magnetic beads enables the use of more antibody isotypes. Read more at: www.emdmillipore.com/HiSens Shaping epigenetics discovery for new or experienced ChIPpers The ChIP protocol is a fundamental tool that has yielded deep insights into epigenetic phenomena. Yet, the technique remains laborious and technically challenging. We have developed a protocol for optimizing the parameters of chromatin fragmentation and preparation for researchers new to studying chromatin biology. Our new, simplified, high-throughput ChIP kit reduces variability and significantly improves signal-to-noise ratios, even for low cell numbers. These Magna ChIP® HiSens kits, combined with the PureEpi™ chromatin prep kit, are particularly suited to new or novice users. Stem Cell Neuroscience Cancer Signaling Cell Structure Epigenetics & Gene Regulation ANTIBODIES, ASSAYS, SMALL MOLECULES, INHIBITORS, AND PROTEINS New VOLUME 2 I 2013 products Magna ChIP® HiSens kits yield better fold enrichment than competitor’s low-input ChIP kits. Sonicated chromatin prepared from 10,000 HeLa cells was chromatin immunoprecipitated using 1 µg of purified IgG (Rabbit IgG: Catalogue No. 12-370) or specific antibodies (H3K4Me3: Catalogue No. 17-614, Phospho- CREB: Catalogue No. 17-10131). Immunoprecipitation of antibody-associated DNA fragments was verified by qPCR using positive control primers (GAPDH promoter primers for H3K4me3 and c-Fos promoter primers for pCREB) and negative control primers (human β-globin promoter primers). Results reflect analysis of 2 µL out of 50 µL total DNA per qPCR reaction. Sonication parameters affect ChIP results! Use the PureEpi™ approach to pinpoint your perfect protocol. Here, ChIPAb+™ Phospho-CREB (Ser133) (Catalogue No. 17-10131) was used for ChIP, using the Magna ChIP® HT96 Chromatin Immunoprecipitation Kit (Catalogue No. 17-10077). ChIP results were analyzed using qPCR and the ΔΔ Ct method to calculate fold enrichment versus an IgG control at the positive locus. PureEpi™ Chromatin Preparation & Optimization Kit Optimized Chromatin Preparation for ChIP Great ChIP data starts with quality chromatin. The PureEpi™ Chromatin Preparation and Optimization kit is the first kit specifically designed to produce high quality chromatin for ChIP experiments. The PureEpi™ kit helps you to avoid chromatin preparation pitfalls and reproducibly generate highly ChIPable chromatin. Discover the PureEpi™ approach and address multiple chromatin isolation and fragmentation parameters that impact ChIP performance. Magna ChIP® HiSens Advantages • Validated, quality-controlled reagents designed to generate high quality chromatin • Easy-to-follow and detailed protocols complete with optimization guidelines for reproducible chromatin preparation. Read more at: www.emdmillipore.com/PureEpi Magna ChIP® HiSens Supplier D 0 200 1000 800 600 400 1200 1400 Fold Enrichment H3K4me3 pCREB H3K4me3 pCREB 0 10 50 40 30 20 60 Fold Enrichment Magna ChIP® HiSens Supplier A 27 2 1248 104 9 29 55 13 1 2 3 4 5 6 0 200 400 600 800 1000 1200 1400 Fold Enrichment 13.38 Fold Enrichment (CREB/IgG) 1293.14 65.27 289.68 499.15 432.53
Transcript
EMD Millipore—with the expertise of Calbiochem®, Chemicon®, and Upstate®
EMD Millipore is a division of Merck KGaA, Darmstadt, Germany
Magna ChIP® HiSens KitsExcellent sensitivity from large or small chromatin amounts These kits combine a complete set of validated reagents with a detailed protocol to create a streamlined, high performance ChIP procedure that allows the use of the same kit for a variety of experimental conditions.
Magna ChIP® HiSens Advantages• ChIP from a wide range of input amounts (10,000 to 1,000,000 cells)• Blended protein A/G magnetic beads enables the use of more antibody
isotypes. Read more at: www.emdmillipore.com/HiSens
Shaping epigenetics discovery for new or experienced ChIPpers The ChIP protocol is a fundamental tool that has yielded deep insights into epigenetic phenomena. Yet, the technique remains laborious and technically challenging. We have developed a protocol for optimizing the parameters of chromatin fragmentation and preparation for researchers new to studying chromatin biology. Our new, simplified, high-throughput ChIP kit reduces variability and significantly improves signal-to-noise ratios, even for low cell numbers. These Magna ChIP® HiSens kits, combined with the PureEpi™ chromatin prep kit, are particularly suited to new or novice users.
ANtIboDIES, ASSAyS, SMAll MolECUlES, INHIbItoRS, AND PRotEINSNewVOLUME 2 I 2013
products
Magna ChIP® HiSens kits yield better fold enrichment than competitor’s low-input ChIP kits. Sonicated chromatin prepared from 10,000 HeLa cells was chromatin immunoprecipitated using 1 µg of purified IgG (Rabbit IgG: Catalogue No. 12-370) or specific antibodies (H3K4Me3: Catalogue No. 17-614, Phospho-CREB: Catalogue No. 17-10131). Immunoprecipitation of antibody-associated DNA fragments was verified by qPCR using positive control primers (GAPDH promoter primers for H3K4me3 and c-Fos promoter primers for pCREB) and negative control primers (human β-globin promoter primers). Results reflect analysis of 2 µL out of 50 µL total DNA per qPCR reaction.
Sonication parameters affect ChIP results! Use the PureEpi™ approach to pinpoint your perfect protocol. Here, ChIPAb+™ Phospho-CREB (Ser133)(Catalogue No. 17-10131) was used for ChIP, using the Magna ChIP® HT96 Chromatin Immunoprecipitation Kit (Catalogue No. 17-10077). ChIP results were analyzed using qPCR and the ΔΔ Ct method to calculate fold enrichment versus an IgG control at the positive locus.
PureEpi™ Chromatin Preparation & Optimization Kit optimized Chromatin Preparation for ChIP Great ChIP data starts with quality chromatin. The PureEpi™ Chromatin Preparation and Optimization kit is the first kit specifically designed to produce high quality chromatin for ChIP experiments.
The PureEpi™ kit helps you to avoid chromatin preparation pitfalls and reproducibly generate highly ChIPable chromatin. Discover the PureEpi™ approach and address multiple chromatin isolation and fragmentation parameters that impact ChIP performance.
Magna ChIP® HiSens Advantages• Validated, quality-controlled reagents designed to generate high
quality chromatin• Easy-to-follow and detailed protocols complete with optimization
guidelines for reproducible chromatin preparation. Read more at: www.emdmillipore.com/PureEpi
Reli(Ab)le.You need more than results. You need results you can reproduce and defend. Every time. Without fail.
Reliable results depend on reliable resources. When you work with reliable antibodies, you can work efficiently and effectively. We guarantee performance because we manufacture performance. We are committed to manufacturing antibodies that perform as specified and as anticipated. Our quality starts at inception and carries through manufacturing, production and distribution, into the lab and onto the bench. From start to finish, we build a platform for reliable performance that provides you with the ultimate confidence in your findings.
Put the most reliable antibodies to work for you.www.emdmillipore.com/Ab
EMD Millipore’s newly released Anti-Puromycin, clone 12D10 and 4G11 monoclonal antibodies (Catalogue Nos. MAbE343 and MAbE342) have been published as part of a powerful and sensitive live cell analysis of protein synthesis: “SUnSET, a nonradioactive method to monitor protein synthesis *”
the authors used these anti-puromycin 12D10 and 4G11 (cited as 2D11) clones to reveal that puromycin was incorporated during protein synthesis, both with internal proteins and with external, type 2 proteins on live cells. they demonstrated that puromycin immunodetection with EMD Millipore’s antibodies is an advantageous alternative to radioactive amino acid labeling, because they enable direct visualization of protein synthesis in individual cells by high-resolution microscopy and may allow the detection of potentially specialized translation areas at subcellular scale, which has not been efficiently achieved until now, even with fluorescent puromycin derivatives. Protein translation can be directly quantified by flow cytometry, even in a subset of cells within larger heterogeneous populations or in cells exposed to pharmacological agents. their further testing on dendritic and t cells demonstrated the potential of SUnSEt for high-throughput drug screening. this technique will have multiple applications in virology, development, host-pathogen interactions, systems/network elucidation and other research areas.
*Schmidt EK et al. Nat Methods. 2009; 6:275-277.
PUblICAtIoN HIGHlIGHt oN NEW ANtIboDIES:
For published studies using this new product, visit: www.emdmillipore.com
For publications on using these small molecules, visit: www.emd4biosciences.com
For published studies using this new product, visit: www.emdmillipore.com
For publications on using these small molecules, visit: www.emd4biosciences.com
New Antibodies, Kits, & Proteins
New Small Molecules & Inhibitors
Description Details Catalogue No.
Epigenetic Regulators Panel - Acetylation A panel containing 18 potent and selective small molecule regulators that is useful for the study of epigenetic acetylation process.
324893-1EA
Epigenetic Regulators Panel - Methylation A panel containing 12 potent and selective small molecule regulators that is useful for the study of epigenetic methylation process.
324894-1EA
Haspin Kinase Inhibitor, CHR-6494 A cell-permeable indazolylimidazopyridazinamine compound that acts as a potent and reversible inhibitor of histone kinase haspin activity (IC50 = 2 nM) with moderate selectivity over TrkA, GSK-3β, PIM1, Cdk1/B and Cdk2/A (% inhibition at 100 nM = 58, 48, 36, 34 and 33, respectively) among a panel of 27-kinases.
372040-10MG
Histone Methyltransferase EZH2 Inhibitor, DZNep
A cell-permeable compound that is shown (at 1 µM concentrations) to inhibit EZH2-mediated trimethylation of K27 on histone H3 and induces the expression of cell-cycle regulatory genes, p21 and p27, as well as the cell death regulator, FBXO32, in OCI-AML3 and HL-60 cells, whereby treatment with inhibitor increases p16 levels in the former, but not the latter of the two cultures.
252790-2MG
Sirt1 Inhibitor VII, Inauhzin A cell-permeable phenothiazine derivative that selectively inhibits SirT1 (IC50 ≤2.0 µM), but not SirT2, SirT3, or HCAC8 (IC50 >50 µM), activity and effectively elevates cellular p53 lysine acetylation (Effective conc. 2 µM), thereby protecting p53 lysine residues from MDM2-mediated ubiquitination without directly inhibiting MDM2 function per se or its activity toward deacetylated p53.
Magna ChIP® HiSens Chromatin Immunoprecipitation Kit
ChIP 17-10460
PureEpi™ Chromatin Preparation and Optimization Kit
ChIP 17-10082
SIRTainty™ Class III HDAC Assay Enzyme Assay 17-10090
the novel SIRtainty™ class III HDAC Assay (Catalogue No. 17-10090) has just been published in a landmark SIRt1 study, headed by David Sinclair’s lab at Harvard University: “Evidence for a common mechanism of SIRt1 regulation by allosteric activators*”
Given that the SIRt1 deacethylase is a promising drug target for age-related disease therapy, the researchers explored the mechanism of sirtuin-activating compounds (StACs) using the SIRtainty™ assay. they found common motifs found in SIRt1 substrates could mediate SIRt1 activation by StACs. the Glu230 residue of SIRt1 was particularly critical for activation. together, the data indicated that SIRt1 can be activated by StACs through an allosteric mechanism.
*Hubbard bP et al. Science Mar 8 2013; 339: 1216-1219.
PUblICAtIoN HIGHlIGHt oN NEW ANtIboDIES:
Haspin Kinase Inhibitor, CHR-6494
EMD Millipore has introduced CHR-6494, a new cell-permeable, potent, and reversible inhibitor of histone kinase Haspin (IC50 = 2 nM) that exhibits moderate selectivity over a variety of kinases, including trkA, GSK-3β, PIM1, Cdk1/b and Cdk2/A. In the recent publication: “Anti-tumor activity of a small-molecule inhibitor of the histone kinase Haspin”
Huertas and colleagues showed that CHR-6494 has a wide spectrum of antitumor properties and can cause cell cycle arrest at the G2/M phase, leading to apoptosis. In addition, they demonstrated that it can reduce phospho histone 3 (thr3) levels in cells and cause metaphase misalignment, spindle abnormalities and centrosome amplification.
Anti-Casper/c-FLIP , clone 17B12.1 Mouse Rt, Hu WB, IHC MABC148
Anti-CIDE-A Rabbit Ms WB, IHC, IF ABC350
Anti-Cyp7a1, clone 15B9.1 Mouse Hu, Rt, Ms WB, IHC MABD42
Anti-Deoxycytidine Kinase, clone 9D4 Mouse Hu WB MABC188
Anti-Ephrin-B2 Mouse Hu, Ms, Rt WB, IHC MABC127
Anti-FLI1 Rabbit Hu WB ABC291
Anti-HSPH1 Rabbit Hu WB, IF ABC264
Anti-hyaluronan synthase 1, clone 12A2.3 Mouse Hu WB, IHC MABC158
Anti-IRGM Rabbit Hu WB, IHC(P), IF ABC338
Anti-LAPTM4B Rabbit Ms, Rt WB ABC290
Anti-MAP1 Rabbit Ms, Hu WB ABC334
Anti-MDC1 Rabbit Hu WB, IC, IP ABC155
Anti-MGEA5 Rabbit Hu WB, IHC, IF ABC283
Anti-MUC-1, EC domain Rabbit Hu WB, IHC(P) ABC159
Anti-NAMPT Rabbit Hu, Ms WB, IHC ABC285
Anti-PDCL Rabbit Hu WB, IHC ABC284
Anti-Smac/Diablo, clone 3A9.1 Mouse Hu WB, IHC MABC174
Anti-Sox5 Rabbit Hu, Ms, Bov, Chicken, Zebrafish
WB ABC115
Anti-STEAP2 Rabbit Hu WB, IHC(P), IF ABC341
New Antibodies, Kits, & Proteins
New Small Molecules & Inhibitors
Description Details Catalogue No.
Ack1 Inhibitor, AIM-100
A cell-permeable furopyrimidine that acts as a potent, ATP-binding site-targeting, Ack1-selective inhibitor (IC50 = 22 nM) and effectively prevents receptor-mediated Ack1 activation (by >90% in MEF & LAPC4 cultures; 16 h 800 nM). Effectively inhibits androgen-independent LNCaP prostate cancer growth both in vitro and in castrated mice in vivo.
104833-10MG
HIF-1 Inhibitor, NSC-134754
A cell-permeable emetan derivative that selectively reduces HIF-1 activity by 73% in a luciferase reporter assay, and blocks HIF-1α protein induction in response to DFX, hypoxia, and IGF-1 in U2OS-HRE-luc cells at 10 µM, without significantly inhibiting cell growth.
400086-5MG
Mirk/Dyrk1B Inhibitor, Compo
A cell-permeable dihydropyridopyrimidine-carboxamide compound that acts as a potent and reversible inhibitor of Mirk/Dyrk1B and Dyrk1A kinases (IC50 = 68 and 22 nM). Shown to induce activation of caspase-3 and sensitize tumor cells to the action of gemcitabine and cisplatin, possibly by de-stabilizing p27.
475857-10MG
PIM3 Kinase Inhibitor VII, M
A cell-permeable hydroxyphenyl-propylidene-benzohydrazide compound that acts as a potent, ATP-competitive (Ki = 0.3 µM), and highly isoform-selective PIM inhibitor (IC50 = 2.5, 2.5, and 0.047 µM against PIM1, PIM2, and PIM3, respectively; [ATP] = 10 µM). Shown to inhibit PIM3-dependent STAT3 Tyr705 phosphorylation in DU-145 prostate cancer and MiaPaCa2 pancreatic cancer cells.
526526-10MG
Sphingosine Kinase 1 Inhibitor, SKI-178
A cell-permeable pyrazolocarbohydrazide compound that acts as a potent, reversible, sphingosine competitive and ATP-non-competitive inhibitor of sphingosine kinase 1 (SphK1) activity with excellent selectivity over SphK2 (Ki = 1.33 and >> 25 µM, respectively). Shown to suppress sphingosine-1-phosphate (S1P) production in A549 cells and efficiently induce apoptosis in several tumor cells.
567732-10MG
STAT3 Inhibitor XVIII, BP-1-102
A cell-permeable, orally bioavailable amidosalicylic acid compound that selectively binds the three subpockets of Stat3 SH2 domain surface (KD = 504 nM) and blocks Stat3 phosphorylation, dimerization, and DNA-binding activity in a dose-dependent manner. Shown to reduce Stat3-dependent growth, survival, migration, and invasion of tumor cells in vitro.
For published studies using this new product, visit: www.emdmillipore.com
For publications on using these small molecules, visit: www.emd4biosciences.com
Description Details Catalogue No.
Adenosine A3 Receptor Antagonist, MRS 1523
A pyridine derivative that acts as a highly selective antagonist of A3 receptor with excellent potency in both humans and rodents (Ki = 18.9 nM for human A3R, and 113 nM for rat A3R).
119152-5MG
D-Amino Acid Oxidase Inhibitor III, AS057278
A cell-permeable pyrazolocarboxylic acid that acts as a selective D-amino acid oxidase (DAO/DAAO/DAMOX/OXDA) inhibitor (IC50 = 910 nM against human DAO; [D-ser] = 10 mM) and effectively protects DAO overexpressing cultures from oxidative stress-induced cell death upon D-Ser (50 mM) exposure (ED50 ≤3.95 µM), while exhibiting little affinity toward NMDAR glycine binding site or inhibitory activity against D-aspartate oxidase (DDO/DSOX).
A cell-permeable hydrazone compound that reversibly binds eukaryotic translation initiation factor 4E (eIF4E; KD = 25 µM) and disrupts eIF4E/eIF4G complex formation. Shown to be brain permeant and reduce neuroligin protein levels, and restore L-LTP threshold and rescue autistic-like behaviours in Eif4ebp2 knockout mice.
324519-5MG
PSD95 Inhibitor, Tat-N-dimer A cell-permeable, dimeric pentapeptide (IETDV) derived from GluN2B C-terminal and linked through a polyethylene glycol (PEG)-based linker that Inhibits the ternary protein complex of PSD-95 (postsynaptic density protein-95), nNOS, and NMDA by directly binding to the tandem PDZ1 and 2 domains of PSD-95 (Ki = 4.6 nM). This inhibition results in the uncoupling between NMDA receptor activity and nitric oxide production.
529542-2MG
Neuroscience (continued)
New Small Molecules & Inhibitors
Signaling
Description Host Species Reactivity Key Applications Catalogue No.
AntibodiesAnti-acetyl-Tip60 (Lys523) Rabbit Hu, Ms, Bov, Por WB 07-1841
Anti-ACVR1C Rabbit Hu WB ABN476
Anti-Caspase-5 Rabbit Hu WB, IC, IF ABS445
Anti-CTRP3 Rabbit Ms WB, IHC, IF ABS451
Anti-GARS Rabbit Hu WB, IHC, IF ABS379
Anti-Gli3, clone 5E1 Mouse Hu, Ms WB, IC, IHC MABS275
Anti-Goosecoid 2 Rabbit Hu, Rt WB, IHC(P) ABS231
Anti-GPR3 Rabbit Hu, Ms WB, IHC, IF ABN473
Anti-LRP6, clone 1C10 Mouse Hu, Rt, Ms WB, IP MABS341
Anti-MIXL1 Rabbit Hu WB, IC ABS232
Anti-NLRP1 Rabbit Hu WB, IHC(P) ABF22
Anti-NLRP12 Rabbit Rt, Hu, Bov WB, FC ABF24
Anti-p115 RhoGEF Rabbit Hu, Ms, Rt WB, IC ABS208
Anti-PDCL Rabbit Hu WB, IHC ABC284
Anti-phospho-P70S6K (Thr470) Rabbit Hu WB ABS431
Anti-phospho-SRPK2(Ser497) Rabbit Hu, Ms, Ham WB ABS192
Anti-Wnt-10b Rabbit Hu WB, IHC ABN475
Proteins & EnzymesUbcH6, active Enzyme Assay 23-036
7a, 25-dihydroxycholesterol A highly potent and specific oxysterol EBI2 (GPR183) agonist with a kd of 450 pM in a saturation binding analysis, and activates EBI2 (EC50=140 pM compared with 2.1nM for its enantiomer 7b,25-OHC) in a GTP-γ assay. Stimulates migration of LPS-activated spleen B cells and T cells in a dose-dependent manner.
128136-1MG
AhR Antagonist III, GNF351 A cell-permeable purine compound that acts as a high-affinity aryl hydrocarbon receptor (AhR) antagonist (IC50=62 nM in mouse liver cytosol expressing humanized AhR) and lacks any agonist activity even at higher doses.
182707-10MG
CXCR3 Agonist, PS372424 A peptidomimetic derivative containing tetrahydroisoquinoline-arginine motif that aligns with a Pro-Arg motif of CXCL10. Acts as a highly specific agonist of human CXCR3 (EC50=1.1 mM, competitive CXCL10 binding IC50=42 nM). Effectively stimulates T-cell migration (~ 50 nM) and blocks the migration of activated T cells towards CXCL11, CXCL12, and CCL5
239823-5MG
ERO1 Inhibitor II, EN460 A cell-permeable thiol reactive enone (EN) compound that selectively interacts with the active-site cysteine of reduced, active form of ERO1α and inhibits its activity (IC50=1.9 µM). Also prevents ERO1 re-oxidation both in vitro and in mouse embryonic fibroblasts. Activates the unfolded protein response and protects ER-stressed 293T cells.
328501-25MG
FtsZ Polymer Stabilizer, PC1 A benzamide ether derivative that exhibits potent bactericidal activity against Staphylococcus aureus and Bacillus subtilis (minimum inhibitory concentration = 0.5 to 1 mg/mL), but does not affect E. coli, yeast, or human hepatocytes. Shown to reduce GTPase activity and induce FtsZ (a prokaryotic homologue of tubulin) polymerization in S. aureus in a dose-dependent manner.
344580-5MG
InSolution™ CFTR Inhibitor II, GlyH-101 A cell-permeable glycinyl hydrazone compound that acts as a potent, selective and reversible open-channel blocker of CFTR with intermediate speed (<1 min; 95% inhibition at 50 µM; Ki = 4.3 µM in CFTR-expressing FRT cells for apical membrane Cl- current) and exhibits desirable aqueous solubility.
219675-5MG
InSolution™ Fluvastatin, Sodium Salt A synthetic, competitive inhibitor of HMG-CoA reductase that acts as anti-hypercholesterolemic agent. Reduces the basal MMP-1 levels in culture media of endothelial cells in a time- and dose-dependent manner.
344096-10MG
InSolution™ HIF-1 Inhibitor A cell-permeable amidophenolic compound that inhibits hypoxia-induced HIF-1 transcription activity (IC50=0.7 and 2.6 µM using AGS and Hep3B cells, respectively, in a reporter assay) by selectively blocking the hypoxia-induced accumulation of cellular HIF-1α protein, while exhibiting no apparent effect on the cellular level of HIF-1α mRNA or that of HIF-1β protein.
400092-5MG
InSolution™ Lovastatin, Sodium Salt Carboxylate form of Lovastatin (Catalogue No. 438185) that is active in whole cells and cell-free assays. Lovastatin is reported to be an anti-hypercholesterolemic agent that acts as a reversible competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase.
438187-5MG
ITK Inhibitor, BMS-509744 A cell-permeable aminothioaryl-thiazolo compound that potently inhibits ITK kinase activity (IC50=19 nM; [ATP] = 1 µM) in an ATP-competitive manner by stabilizing ITK activation loop in a substrate-blocking, inactive conformation, inhibiting Fyn, IR, Lck, Btk only at much higher concentrations (IC50 ≥1.1 µM) and exhibiting little or no activity against 14 other kinases (IC50 ≥11 µM).
419820-5MG
Ketohexokinase Inhibitor An orally bioavailable pyrimidinopyrimidine compound that acts as a potent, reversible and ATP-competitive inhibitor of human hepatic KHK activity (KHK-C isoform; IC50 = 12 nM in a transcreener ADP assay) and efficiently blocks fructose-1-phosphate secretion (IC50 ≤ 400 nM in HepG2 cells).
420640-10MG
PDE10A Inhibitor, Cpd15 A cell-permeable pyrazoloquinoline compound that acts as a potent phosphodiesterase 10A inhibitor (Ki≤5 nM against human PDE10A), while exhibiting >500-fold selectivity over other human PDEs 1-11 and little activity against CYP3A4 (IC50 >20 µM) or a panel of 23 kinases (IC50 >30 µM).
Proprotein Convertase Inhibitor A cell-permeable tripeptide derivative containing an Arg-X-Arg motive that acts as a highly potent and reversible furin inhibitor (Ki=16 pM). Also shown to inhibit several other pro-protein convertases, such as PC1/3, PC4, PAEC4, PC5/6 with almost similar potency.
537076-2MG
PTP Inhibitor XXXI, II-B08 A cell-permeable indolo-salicylic acid compound that is shown to target SHP2 catalytic domain and inhibit SHP2-catalyzed pNPP hydrolysis (IC50=5.5 µM) in a reversible and non-competitive manner (Ki=5.2 µM). Effectively blocks hyperproliferative activity of human hematopoietic progenitor cells, as well as c-kit-dependent, SHP2-mediated myeloid proliferation.
565852-10MG
TLR4 Inhibitor, TAK-242 A cell-permeable cyclohexenecarboxylate that disrupts TLR4, but not TLR1-3 or TLR5-10, interaction with adaptor molecules TIRAP and TRAM via direct binding to TLR4 intracellular Cys747 residue.Shown to effectively inhibit TLR4-mediated cellular events (IC50=1.8, 1.3, and 1.9 nM, respectively, against LPS-induced NO, IL-6, and TNF-α production in murine RAW264.7 macrophages) in vitro.
614316-5MG
New Small Molecules & Inhibitors
tlR4 Inhibitor, tAK-242
EMD Millipore has recently introduced TAK-242, a new cell-permeable, fast acting, non-toxic compound that selectively blocks TLR4 signaling via binding to its intracellular domain and inhibits the production of multiple cytokines. TAK-242 selectively modifies Cys747 of TLR4 TIR (Toll/IL-1 receptor) and inhibits the interaction of TIRAP and TRAM with TLR4 in a dose-dependent manner. In the paper: “tAK-242 (resatorvid), a small-molecule inhibitor of toll-like receptor (tlR) 4 signaling, binds selectively to tlR4 and interferes with interactions between tlR4 and its adaptor molecules*”
Matsunaga et al from Takeda Pharmaceuticals demonstrated that TAK-242 binds selectively to TLR4 and subsequently disrupts the interaction of TLR4 with adaptor molecules, thereby inhibiting TLR4 signal transduction and its downstream signaling events. They also show that it inhibits the TIRAP-mediated activation of NF-κB.
*Matsunaga, N., et al. Mol. Pharmacology 2011; 79: 34-41.
PUblICAtIoN HIGHlIGHt oN SMAll MolECUlES:
Secondary & Control Antibodies
Stem Cell Research
Description Host Species Reactivity Key Applications Catalogue No.
AntibodiesAnti-HSV•Tag®,cloneHSV78 Mouse All WB MAC123
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