Program - Society of Toxicology

50 th Anniversary Annual Meeting and ToxExpo
Program Description (Continued)
MONday
Abstract # Abstract #
#848 2:36 MINIMUM MATERIAL
CHARACTERIZATIONS FOR
NANOTOXICOLOGY STUDIES: A
NECESSITY OR A NUISANCE? ​N. J. Walker.
National Toxicology Program, NIEHS, Research
Triangle Park, NC.
#849 3:02 THE SELECTION AND
CHARACTERIZATION OF
NANOMATERIALS FOR DEVELOPING
TOXICOLOGICAL QSARS. ​S. Oldenburg 1 , A.
Neigh 1 , O. Nguyen 1 and S. Ali 2 . 1 nanoComposix, San
Diego, CA and 2 NCTR /U.S. FDA, Jefferson, AR.
#850 3:28 DOSIMETRIC CONSIDERATIONS FOR
EXPLORING THE CYTOTOXICITY OF
SILICA NANOPARTICLES IN VITRO. ​
D. F. Lison 1 , V. Rabolli 1 and L. Thomassen 2 .
1
Louvain Centre for Toxicology and Applied
Pharmacology, Brussels, Belgium and 2 Centrum
voor Oppervlaktechemie en Katalyse, Katholieke
Universiteit Leuven, Leuven, Belgium.
#851 3:54 ENABLING PREDICTION AND
EXTRAPOLATION: A NEW PARADIGM FOR
NANOMATERIAL DOSIMETRY IN VITRO. ​
J. G. Teeguarden 1 , P. M. Hinderliter 2 , G. Orr 3 , K. R.
Minard 2 , B. D. Thrall 2 and J. G. Pounds 2 . 1 Biological
Monitoring and Modeling, Pacific Northwest
National Laboratory, Richland, WA, 2 Biological
Sciences, Pacific Northwest National Laboratory,
Richland, WA and 3 Environmental and Molecular
Sciences Laboratory, Pacific Northwest National
Laboratory, Richland, WA.
4:20 PANEL DISCUSSION/Q&A.
Monday Afternoon, March 7
2:00 PM to 4:45 PM
Room 144
Workshop Session: Understanding Structural and Physical
Chemical Drivers of Drug Toxicity: Utility and Translatable
Value
Chairperson(s): Dylan Hartley, Genentech, South San Francisco, CA,
and Manfred Kansy, F. Hoffman-LaRoche, Basel, Switzerland.
Sponsor:
Drug Discovery Toxicology Specialty Section
Endorsed by:
Biological Modeling Specialty Section
In Vitro and Alternative Methods Specialty Section
Given the demands on drug discovery teams to produce effective, specific,
and safe new molecules, toxicologists are now finding themselves with
new responsibilities in the drug discovery setting as part of lead optimization
teams. To be effective members of these teams, toxicologists are
now required to gain awareness and experience in recognizing potential
structural and physicochemical properties of compounds that often lend to
certain off-target toxicities, such as off-target receptor activities, QT-interval
prolongation, phospholipidosis, enzyme induction, liver injury, and genotoxicity.
The understanding of structural attributes of compounds that may
drive specific liabilities will enhance the toxicologist’s contributions by
enabling active collaboration with chemists to inform synthesis of new
molecules to gain a safety advantage over previous molecules. To this
end, in vitro assays (e.g., hERG channel inhibition, pharmacology ligand
binding panels, enzyme induction, and transporter inhibition), coupled with
specific mathematical or statistical models, and pharmacophore models
(e.g., hERG channel and PXR activation) can be effective at instructing
chemical modifications to attenuate the potential for activity against specific
toxicological endpoints a priori. Furthermore, new in silico approaches in
chemoinformatics are proving useful for predicting off-target polypharmacology
by mapping potential drug-target interactions through ligand-based
similarities. Similarly, mapping adverse drug reactions to chemical space
may hold promise for predicting specific features of compounds that lead to
adverse drug reactions in humans. Finally, detailed assessments of pharmacokinetic
or physical chemical drivers of tissue accumulation are improving
our understanding of in vitro—in vivo correlations. Overall these approaches
demonstrate the importance and utility of understanding structural motifs
and physicochemical properties of compounds that lead to off-target activity.
#852 2:00 UNDERSTANDING STRUCTURAL AND
PHYSICAL CHEMICAL DRIVERS OF DRUG
TOXICITY: UTILITY AND TRANSLATABLE
VALUE. ​D. P. Hartley 1 and M. Kansy 2 . 1 Genentech,
South San Francisco, CA and 2 F. Hoffmann-LaRoche
AG, Basel, Switzerland.
2:00 INTRODUCTION. ​Dylan Hartley
#853 2:05 CLINICAL TRANSLATIONAL VALUE OF
PHARMACOLOGICAL PROMISCUITY
OBSERVED IN IN VITRO SAFETY
PROFILING. ​L. A. Urban 1 , S. Whitebread 1 , J.
Hamon 2 , K. Azzaoui 2 and D. Mikhailov 1 . 1 Center
for Proteomic Chemistry, NIBR, Cambridge, MA
and 2 Center for Proteomic Chemistry, NIBR, Basel,
Switzerland.
#854 2:37 PREDICTING DRUG OFF-TARGETS
UNDERLYING ADVERSE EVENTS. ​
M. Keiser 1,2 and B. Shoichet 2 . 1 SeaChange
Pharmaceuticals, Inc., San Francisco, CA and
2
Pharmaceutical Chemistry, University of California,
San Francisco, San Francisco, CA. Sponsor: D.
Hartley.
#855 3:09 EARLY SAFETY PROFILING IN DRUG
DISCOVERY: HOW STRUCTURAL AND
PHYSICOCHEMICAL COMPOUND
CHARACTERISTICS INFLUENCE THE
SAFETY PROFILE OF DRUG CANDIDATES. ​
M. Kansy and H. Fischer. Nonclinical Safety, F.
Hoffmann-La Roche Ltd., Basel, Switzerland.
#856 3:41 PHARMACOKINETIC DRIVERS OF
TOXICITY FOR SMALL MOLECULES:
EVALUATING PLASMA-TISSUE
CONCENTRATION RELATIONSHIPS. ​D.
Diaz. Investigative Safety Assessment, Genentech,
South San Francisco, CA.
#857 4:13 MAPPING ADVERSE DRUG REACTIONS IN
CHEMICAL SPACE. ​J. Scheiber. Pharmacology
Research & Early Development Informatics,
Disease & Translational Informatics, Pharmacology
Research and Early Development (pRED), Penzberg,
Germany. Sponsor: D. Hartley.
188
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