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The use of the IV microtracer technique to drive formulation optimisation
Vanessa Zann, Paul Dickinson, Wang Wang Lee, George Kirk, Owen Jones, Andy Gray, Davindera Singh Sanghera, Mark Seymour, Jo Collier, Lloyd Stevens, Julie Dent

Strategy: Use IV microtracer techniquer to de risk compounds with PK issues and drive formulation development

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Addressing the challenges of poor solubility: Rapid development and clinical evaluation of a lipid based formulation to enhance oral bioavailability of amuvatinib (MP-470)
P.D. Scholes, J. McDermott, J. Vertommen, J-L Colin, G Choy, M Azab, R Joshi and S. Redkar

Physiochemical and biopharmaceutical properties of new chemical entities are presenting increasing challenges to successful oral drug delivery. Here we present data on amuvatinib, a novel multi-targeted tyrosine kinase inhibitor specifically designed to be a potent inhibitor of mutant c-Kit and PDGFRalpha.

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Elucidation of the Relative Bioavailability of a Drug Candidate from Different Regions of the Human Gastrointestinal Tract
David Harris, Ph.d. , Joanne Collier, MBCHB, Alyson Connor, Ph. D. , Tomoko Freshwater, Ph. D. , David Goldfarb, Ph. D. , Ann Horowitsz Ph. D. , Xuewen Ma, Ph. D. , Paul Statkevich, Ph. D.

This poster describes a pharmacokinetic study to investigate the relative absorption of an NCE from different regions of the human gastrointestinal tract, to support potential development of a sustained-release formulation.

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Evaluation Of Single Point And IC50 Shift Assays For Measuring Time-Dependent Inhibition Of Drug Discovery Compounds
Katie Fox, Rosey Pearson, Phillip Butler, Clive Dilworth

The aim of this study is to evaluate different assay designs, and data analysis methodology for measuring the extent of TDI for known inhibitors. We propose a reversible inhibition and TDI screening platform to cover early phase compounds, which enables accurate decisions to be made regarding development of compounds which could cause DDIs.

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GALAS Modeling Methodology Applications in the Prediction of the Drug Safety Related Properties
Andrius Sazonovas, Remigijus Didziapetris, Justas Dapkunas, Liutauras Juska, Pranas Japertas

Early computational evaluation of drug candidate properties related to its pharmaceutical safety (such as hERG inhibition induced cardiotoxicity or CYP3A4 inhibition responsible various unwanted drug-drug interactions) is becoming increasingly important in the drug discovery process.

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Probabilistic Predictive Model of the Human Liver Microsomal Metabolism Regioselectivity
Justas Dapkunas, Andrius Sazonovas, Pranas Japertas

Analytical identification of metabolites for a drug candidate is usually a time consuming and low-throughput task which is performed only in late drug development phases.Therefore, the ability to predict possible sites of human liver microsomal metabolism using in silico techniques would be highly beneficial for any medicinal chemist.

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Mechanistic Prediction of Volume of Distribution: The Influence of Plasma and Tissue Binding
Kiril Lanevskij, Remigijus Didziapetris, Pranas Japertas

Plasma protein binding (usually expressed as a percentage bound fraction %PPB) and volume of distribution (Vd) are the two major parameters characterizing drug disposition in the body.

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Nitric Oxide Decreases the Expression and Activity of the Ubiquitin-Conjugating Enzyme UbcH10
Nick D. Tsihlis, PhD, Chris S. Oustwani, BA, Ashley K. Vavra, MD, Qun Jiang, MD and Melina R. Kibbe, MD

Nitric oxide (NO) has been shown to limit the formation of neointimal hyperplasia in animal models of arterial injury. Ubiquitination proceeds via formation of thioester bonds and NO can act to disrupt those bonds. We report that NO decreases the activity and expression of UbcH10 in vitro, and decreases the expression of UbcH10 following arterial injury in vivo. Therefore, UbcH10 may be a promising therapeutic target for inhibiting neointimal hyperplasia.

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High-Throughput Multiplexed Assay for Analysis of Hematopoietic Stem Cells Differentiation and Hematopoietic Toxicity
Oksana Sirenko*1, Pierre Turpin1, Yen-Wen Chen1, Jayne Hesley1, Juan L. Almara2, Daniel Zimmerman2, David Novo2, H. Roger Tang1, and Evan F. Cromwell1

Hematopoietic stem cells (HSCs) give rise to all the blood cell types and are important for cell therapy and drug development. During the development of lymphoid and myeloid lineages, HSC differentiate into committed hematopoietic progenitors. Monitoring the expansion and differentiation of HSCs into lineage-commited hematopoietic progenitors is important for research of hematopoiesis and developing therspeutic processes with HSCs

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Showing Results 41 - 50 of 111
Scientific News
Microscopic “Walkers” Find Their Way Across Cell Surfaces
Technology could provide a way to deliver probes or drugs to cell structures without outside guidance.
Revalesio’s Drug Shows Promise in Treating Alzheimer’s
Multiple published research studies outline the potential for RNS60 to effectively treat Alzheimer’s disease by protecting neuronal function and restoring neuronal plasticity.
Getting Metabolism Right
Analysis of 89 models of metabolic processes finds flaws in 44 of them — but suggests corrections.
Persistent Pharmacokinetic Challenges to Pediatric Drug Development
Current knowledge of rational drug dose adjustments is limited, greater effort needs to be made to determine ontogenic factors that influence ADME.
‘Tissue Chip’ to Screen Neurological Toxins
UW-Madison team are developing a faster, more affordable way to screen for neural toxins.
Promise for Treatment of Pancreatic Cancer
Ultrasound microbubbles can improve tumor absorption of cancer drugs.
Animal Testing can Mislead Drug Discovery and Development
Several blockbuster drugs would not be on the market, if scientists had relied solely on drug-uptake in animal trials, according to new research.
Marijuana Compound May Offer Treatment for AD
Extremely low levels of the compound in marijuana known as delta-9-tetrahydrocannabinol, or THC, may slow or halt the progression of Alzheimer’s disease.
New Advances in the Pre-clinical Evaluation of Hepatitis B Therapies
Imperial College London to present first public HBV Data from CN Bio in vitro liver model.
ADME of Antibody-Maytansinoid Conjugates
Continued understanding of the ADME properties of ADCs entering clinical evaluations should provide additional insight into attributes that may be necessary for clinical success.
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