|A Simple, Robust Automated Multiplexed Cell-Based Assay Process for the Assessment of Mitochondrial Dysfunction and Cytotoxicity|
Brad Larson, Peter Banks, Tracy Worzella, Andrew Niles and Timothy Moeller
Recent studies have shown that an increasing number of drugs no longer on the market have negative effects on mitochondrial function in key organs such as the liver and heart. Therefore it is increasingly important to monitor the effects of lead compounds on mitochondrial function in relevant cell systems. The ability to incorporate a simple, rapid, multiplexed, predictive assay can make the detection of potential toxic effects easier to perform early on in the drug discovery process.
|An Automated, Cell-based Platform for the Rapid Detection of Novel Androgen Receptor Modulators|
Brad Larson, Bruce Sherf (INDIGO Biosciences), and Peter Banks
The Androgen Receptor (AR) is a member of the family of nuclear receptors responsive to steroid hormones. This poster aims to devise, validate and perform a preliminary automated HTS screening campaign to identify novel modulators of AR activity.
|Validation of an Automated Cell-Based Bioluminescent TNFa Blocker Bioassay|
Brad Larson, Tracy Worzella, Rich Moravec, Neal Cosby, Frank Fan, Teresa Surowy and Peter Banks
TNFa blocker biopharmaceuticals represent an important and successful class of protein drugs used in the treatment of several autoimmune diseases. Bioassays are indispensible tools in biopharmaceutical drug development and commercialization that are used to quantify biological activity and stability of drugs or drug candidates. The automation of these assays can serve to create an accurate, robust process which can allow the researcher to perform other more important functions.
|Automation of a Generic Fluorescence Methyltransferase Activity Assay|
X. Amouretti, P. Brescia, P. Banks, G. Prescott, Meera Kumar
Epigenetic processes are attracting considerable attention in drug discovery as their fundamental roles in controlling normal cell development and contributions to disease states become more clearly defined. This work combines a fluorescence-based assay with liquid handling and dispensing instrumentation and a multi-mode reader which can be used to monitor the biological activity of the histone methyltransferase (HMT) G9a, a model system.
|Modeling Disposition of Sotalol following Intravenous and Oral Administration in Healthy Adult Subjects|
S. Ray Chaudhuri, V. Lukacova and W. S. Woltosz
Sotalol is a non specific adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmia. Its absorption, distribution and systemic PK or, collectively, ‘disposition’ was modeled and simulated using GastroPlus™ v7.0. Biopharmaceutical properties were obtained from in silico predictions and in vitro measurements.
|Predicting hERG Potassium Channel Affinity with Artificial Neural Network Ensembles|
Adam C. Lee, GrazynaFraczkiewicz, Robert Fraczkiewicz, Robert D. Clark and Walter S. Woltosz
Modeling hERG inhibition has gained significant popularity since 2005, when the FDA recognized the correlation between hERG inhibition and a prolonged QT interval by issuing guidance for the evaluation of new non-antiarrythmic drugs against the hERG channel.Long QT syndrome or LQTS is a risk factor for ventricular tachyarrhythmias and sudden death.
|Predicting Sites of Metabolism with Artificial Neural Network Ensembles|
Marvin Waldman, Robert Fraczkiewicz, JinhuaZhang, Robert D. Clark and Walter S. Woltosz
Hepatic first-pass metabolism of many drugs and pro drugs plays a key role in their oral bioavailability. The human cytochrome P450 enzymes are responsible for the metabolism of most drugs. Knowledge of likely sites of metabolic attack in a drug molecule can aid in designing out unwanted metabolic liabilities early on in the drug discovery process, as well as in the design of pro drugs where metabolic transformation is desired.
|GALAS Modeling Methodology Applications In The Prediction Of Drug Metabolism Related Properties|
Remigijus Didziapetris, Justas Dapkunas, Andrius Sazonovas and Pranas Japertas
Analytical identification of metabolites for a drug candidate is usually a time consuming and low-throughput task and is performed only at the later phases of drug development. Therefore the possibility to predict possible sites of human liver microsomal (HLM) metabolism using in silico techniques would be a very attractive feature for any medicinal chemist.
|Effective Use of In-Silico Tools in Lead Optimization|
Pranas Japertas, Andrius Sazonovas and Kiril Lanevskij
Of all the challenges facing medicinal chemists in general, one of the most significant must be transforming an active molecule into a viable drug. Lead optimization efforts are guided by a combination of factors, such as potency, ease of synthesis, patentability concerns, specific synthetic constrains of the interaction with the target, as well as the lead’s toxicity and ADME properties.