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High-Throughput Campaign to Identify Reversible Small Molecule Inhibitors of p97
Kelin Li, Tsui-Fen Chou, Kevin Frankowski, Brian E. Nordinc, Patrick Porubsky, Mathew P. Patricellic, Han-Jie Zhou, Sam Gerritz, Raymond J. Deshaies, Jeffrey Aubé, Frank J. Schoenen*

The AAA ATPase p97 is a critical factor in maintaining protein homeostasis in eukaryotic cells. Two probe compounds ML240 and ML241 were developed that both inhibit p97 ATPase activity with an IC50 of approximately 100 nM, and block degradation of p97-dependent proteasome substrate with an IC50 of approximately 900 nM and 3500 nM, respectively. They specifically targeted p97, exhibited markedly different potencies for activating executioner caspases and blocking cell growth.

Using the Promega GloSensor™ cAMP technology on the FLIPR® Tetra system for live cell Gi- and Gs- coupled GPCR second messenger assays
J. Pschorr, S. Lydford, C. Crittenden and Y.-W. Chen

Detection of Gs- and Gi-coupled GPCR second messenger signal activity has been traditionally accomplished using endpoint assays such as radioactive binding or cAMP assays that require cell lysis. This poster demonstrates the use of the modified luminescent firefly luciferase-based Promega GloSensor™ cAMP Assay on the FLIPR® Tetra system to enable detection of cAMP mediated Gs- and Gi-coupled GPCR activity in a true kinetic assay.

Neurotoxicity Assays Using iPSC-Derived Neurons and High Content Imaging
Oksana Sirenko, Susan DeLaura, Lucas Chase, Jayne Hesley and Evan F. Cromwell

Neurotoxicity can cause temporary or permanent damage of brain or peripheral nervous system and has been found to be a major cause of neurodegenerative diseases such as Alzheimer’s or Parkinson’s. Accordingly, there is a great interest in developing more predictive, disease relevant cell-based models and efficient screening tools for assessing the neurotoxicity of chemical compounds, drug candidates and environmental agents.

SpectraMax® Microplate Readers: A complete solution for Transcreener® assays
Cathleen Salono, Caroline Cardonnel, Kasia Proctor and Cathy Olsen

Transcreener® ADP2 Assays are homogenous assays with fluorescent readouts that enable the detection and screening of established drug targets including protein and lipid kinases, as well as emerging targets such as carbohydrate kinases, triphosphatases, heat shock proteins and other ATPases.

Live Cell Beating Assay Using Human iPSC-derived Cardiomyocytes for Evaluation of Drug Efficacy and Toxicity
Oksana Sirenko, Carole Crittenden, Blake Anson, Jayne Hesley, Yen-Wen Chen, Nick Callamaras and Evan F. Cromwell

A large percentage of new drugs fail in clinical studies due to cardiac toxicity. Development of highly predictive in vitro assays suitable for screening, safety assessment or other environments is therefore extremely important for drug development. Human cardiomyocytes derived from stem cell sources can greatly accelerate the discovery of cardiac drugs and improve drug safety by offering more clinically relevant cell-based models than those presently available.

Identification of novel autoantigensin patients with liver autoimmune diseases by Protein MicroArray
C. Zingaretti1, M. Arigò1, A. Cardaci1, A. Sinisi1, L. Muratori3, P. Colombatto4, F. Bonino2, P. Invernizzi5, , A.L. Zignego6 MC. Crosti1, M. Moro1, J. Geginat1, Pagani M.1, R. De Francesco1, S. Abrignani1. & M. Bombaci1

The characterization of autoimmune disease-specific biomarkers are of primary importance for the development of diagnostic tools and the comprehension of pathogenetic mechanisms leading to autoimmunity. To this aim a protein microarray was employed to analyze serum samples from patients with autoimmune hepatitis (e.g. AIH & PBC) and of healthy as controls. A panel of autoantigens able to discriminate among the groups of patients was identified for potential use as biomarkers.

Attempts of facilitated DelF508-CFTR trafficking to the plasma membrane
Sergey Shityakov, Massimo Micaroni, Alexander A. Mironov, Alberto Luini

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the CF transmembrane conductance regulator protein (CFTR), a cAMP-regulated chloride channel. One of the most common CFTR mutations is the deletion of phenylalanine in 508 position (DelF508-CFTR). This mutation induces small conformational change hence the CFTR trafficking is no more effective. The main idea is to find a molecule to facilitate the DelF508-CFTR trafficking to the plasma membrane.

Production of Naturally Compressed Screening Arrays
Steven A Trim.

Animal venoms and toxins are a rich source of novel biologics with several making the progression from tool to therapeutic such as FDA approved Integrilintm (Eptifibatide) (Millennium pharmaceuticals)1 derived from Rattlesnake venom for unstable angina.

A fast and fully automated solution for Lipidic Cubic Phase (LCP) screening using mosquito LCP
Joby Jenkins1, Patricia Edwards2, Rob Lewis1and Joanne Franklin1

Membrane proteins, such as G-protein-coupled receptors, are known to be much more difficult to purify and crystallise than soluble proteins due to their native environment within the lipid bilayer of the cell membrane. The in meso (lipidic cubic phase or LCP) crystallisation technique has revolutionised the process of crystallising membrane proteins. This method utilises highly viscous lipid mesophases to contain the membrane proteins for crystallisation.

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Showing Results 51 - 60 of 257
Scientific News
Cancer-Fighting Drugs Might Also Stop Malaria Early
A number of compounds have been identified which could be used to fight malaria.
Bowel Disease Gene Discovery
Genetic changes that occur in patients with the bowel condition Crohn’s disease could hold clues to fighting the illness.
Test Reliably Detects Inherited Immune Deficiency in Newborns
NIH-supported study suggests that early diagnosis of severe combined immunodeficiency leads to high survival rates.
Test Reliably Detects Inherited Immune Deficiency in Newborns
NIH-supported study suggests that early diagnosis of severe combined immunodeficiency leads to high survival rates.
Heart Molecule Discovery Could Lead to Effective Treatment for Heart Failure
Researchers have discovered a previously unknown cardiac molecule that could provide a key to treating, and preventing, heart failure.
UK Government Must Do More to Reduce Risk of vCJD Infection
Report recommends that UK Government commission a full assessment of the risks currently faced by the UK blood supply.
NIST Instrument Enables High-speed Chemical Imaging of Tissues
Researchers have demonstrated a dramatically improved technique for analyzing biological cells and tissues based on characteristic molecular vibration "signatures."
Innovative Technology Enables First Crystal Structure of mGlu5 Transmembrane Domain to be Determined
Several novel drug candidates have been identified to help treat specific neuropsychiatric disorders.
Capturing Cancer: A Powerful New Technique for Early Diagnosis
Researchers describe an innovative technique for early disease detection, which they call immunosignaturing.
Significant Step Towards Blood Test for Alzheimer's
Scientists have identified a set of 10 proteins in the blood which can predict the onset of Alzheimer’s, marking a significant step towards developing a blood test for the disease.
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