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Bioluminescent Approaches for In Vitro ADMET
James J Cali, Mary Sobol, Dongping Ma, Michael Valley

Bioluminescent ADMET assays couple targets of interest to the photon emitting reaction of firefly luciferase. Multiplexed cell-based assays measure compound cytotoxicity and induction of P450 transcription and enzyme activity. Cell-free membrane assays measure P450 or monoamine oxidase enzyme activities and their inhibition by test compounds.

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Initiatives For The Sharing Of Toxicity Data
Katharine Briggs

Much high-quality toxicity information is held within organisations rather than being in the public domain. Organisations would benefit from sharing this data with each other in a reciprocal manner where commercial sensitivity issues allow.

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MS-Xelerator™: Advanced Algorithms for LC/MS Data Processing Applied to Biomarker Discovery, Differential Analysis and Quantitative Proteomics
M.M.A. Ruijken

LC-MS based proteomic experiments are used to compare complex biological samples across multiple conditions. Fast, powerful computational tools are needed to explore and detect differences in the areas of Expression Proteomics and Biomarker Discovery. In general, specialized steps are necessary to solve these difficult problems (binning, alignment & normalization, peak picking, relative quantitation, etc.). MS-Xelerator is a collection of software tools dedicated to all of the above tasks.

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A Robust High Throughput Physicochemical Screen for Phospholipidosis
Pavol Vitovic, Juha-Matti Alakoskela and Paavo K.J. Kinnunen

The poster presents a simple HT physicochemical screen, predicting PLD in real-time by surface activity profiling (using Kibron Delta-8 analyzer). The results are equal or better than derived from a cell based assay, throughput is up 450 compounds/24 hrs and drug consumption < 1 mg/compound.

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Promega’s Multiplexed Cell Viability and Apoptosis Assays Performed on the PHERAstar
Tracy Worzella and Brad Larson

Today’s high-throughput screening facilities face increasing demands to generate more information from their existing compound libraries. In this poster, we demonstrate the combination of several Promega cell-based assays (CellTiter-Blue®, Apo-One® and Caspase-Glo® 3/7) multiplexed in both low-volume 384 and 1536-well plate formats. The BMG LABTECH PHERAstar microplate reader is used to record both luminescence and fluorescence, depending on the multiplex combination.

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Promega’s Multiplexed Luciferase Reporter and Cell Viability Assays performed on the PHERAstar
Tracy Worzella and Brad Larson

By multiplexing a reporter assay (EnduRen™, ViviRen™) with a cell viability assay (CellTiter-Glo®), it is possible to determine if reporter response variations are due to changes in cell number and health. In this poster, we demonstrate the combination of several Promega cell-based assays multiplexed in both low-volume 384- and 1536-well plate formats using the BMG LABTECH PHERAstar microplate reader to record luminescence.

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Metabolic Stability and Clearance of Pharmaceutical Chemicals in Pre-Pooled Cryopreserved Hepatocytes
Aruna Koganti, Nicola J. Hewitt, Wei Zhang, Michael Cheseborough, Christopher M. Terrell, Paul M. Silber and Charles B. Jensen

Cryopreserved hepatocytes express both phase I and phase II enzymes and facilitate early evaluation of the metabolic stability of pharmaceuticals. Availability of pre-pooled cryopreserved hepatocytes further enhances the utility of this model by reducing donor to donor variability. In this study, the metabolic stability of 29 pharmaceutical compounds were evaluated in pre-pooled cryopreserved human hepatocytes.

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CYP4F Enzymes are the Major Enzymes in Human Liver Microsomes that Catalyze the O-Demethylation of the Antiparasitic Prodrug DB289
Greg Loewen, Michael Zhuo Wang, Janelle Saulter, Etsuko Usuki, Yen-Ling Cheung, Michael Hall, Arlene Bridges, Oliver Parkinson, Chad Stephens, James Allen, Darryl Zeldin, David Boykin, Richard Tidwell, Mary Paine, James Hall and Andrew Parkinson

DB289 is a prodrug that is converted by several steps to the active metabolite DB75. DB289 exhibits enhanced oral efficacy and reduced acute toxicity over DB75, an aromatic dicationic compound that is effective against a broad range of pathogens in vitro including African trypanosomiasis (African sleeping sickness). This reaction phenotyping study aimed to identify the enzymes responsible for oxidative O-demethylation; the first step in this conversion to DB75.

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Effects of Gender, age and Ethnicity on Human Cytochrome P450 Activity
Lisa Collins, L. Anne Dwyer, Zell Woodworth, Tiffin Ramsey, Clayton Otwell, Chad Pope, Stephanie Helmstetter, Terry Graves, Josh Snyder, Jason Barricklow and Andrew Parkinson

The expression of CYP enzymes is influenced by both endogenous and exogenous factors. The aim of this analysis was to evaluate whether the age, gender, or ethnicity of the donor should influence the selection of human liver microsomes for drug metabolism studies, as well as whether cigarette smoking and alcohol consumption are reliable indicators of elevated CYP1A2 and CYP2E1 activity, respectively.

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Scientific News
Quotient Clinical Completes Innovative First-In-Human Program
First-in-human clinical program designed to develop an optimal oral formulation.
Neuropsychiatric Drug Candidate Shows Good Safety & Tolerability
Transition Therapeutics announces results from Phase 1 AME & renal clearance clinical studies of neuropsychiatric drug candidate ELND005.
IUPUI Chemist Earns Grant to Improve Drug Screening in Forensics
$273,826 award to improve the speed and accuracy of mass spectrometry for detecting drugs and poisons.
Hearts On A Chip To Aid Drug Screening
UC Berkeley bioengineers have developed a heart-on-a-chip which can be used for drug safety screening.
Using Human Stem Cells To Identify Dangerous Side Effects Of Drugs
Scientists have developed a test that uses cells from a single donor's blood to predict whether a new drug will cause a severe reaction in humans.
3-D Engineered Bone Marrow Makes Functioning Platelets
Scalable model supports patient-specific treatments, advanced study of blood disorders.
Single-Cell, 42-plexed Protein Analysis Achieved with a New Microchip Technology
A novel microdevice capable of detecting 42 unique immune effector proteins has been developed.
Mini Synthetic Organism Instead Of Test Animals
Using a compact multi-organ chip, and those of three separate microcircuits, researchers can study the regeneration of certain kidney cells.
Novel Organoid Matrix Enables Long-Term Culture of Human Hepatocytes
Organoid growth matrix to enable long-term culture of genome-stable bipotent stem cells from adult human liver.
First Contracting Human Muscle Grown in Laboratory
Researchers at Duke University report the first lab-grown, contracting human muscle, which could revolutionize drug discovery and personalized medicine.
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