From: chemistry-request at ccl.net
To: chemistry-request at ccl.net
Date: Wed Feb 1 09:50:19 2006
Subject: 06.06.04 Applying Mechanisms of Chemical Toxicity to Predict Drug Safety, WASHINGTON, D.C
Applying Mechanisms of Chemical Toxicity to Predict Drug Safety
JUNE 4 6, 2006 | OMNI SHOREHAM | WASHINGTON, D.C.
http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html?DOC=acsprospectives%5c06toxicity%5cindex.html
Today, pharma discovery scientists have the benefit of excellent
chemistry and often a wealth of drug candidates to choose from.
Many, if not most drug candidates fail due to toxicology issues,
so chairs Prof. F. Peter Guengerich, Professor of Biochemistry and t
he Director of Vanderbilts Center in Molecular Toxicology, and
Dr. James MacDonald, EVP of Preclinical Development at the
Schering-Plough Research Institute, specifically organized
this conference to aid industry scientists in the early prediction
of which candidates will prove toxic.
The conference will discuss basic and practical issues of chemical
tox as well as newer technologies. It will also cover what systems
have proven most useful in prediction, and how information can be best
used in the regulatory process. The sessions are designed to encourage
discussion and audience participation and are arranged around the
topics of:
Mechanisms of Chemically Induced Toxicity:
* Prof. Sidney Nelson of the University of Washington will speak
on structural alerts in medicinal chemistry and the science of
reactive metabolites
* Prof. Timothy Macdonald of the University of Virginia will speak
on felbamate and other problem drugs and the roles that reactive
metabolites play in toxicity
* Dr. David Evans of Johnson & Johnson will speak on the application
of covalent binding screening and its usefulness in decisions
* Dr. David Thompson of Pfizer will speak on contexts of drug
toxicity and the extents of contribution of major mechanisms
including reactive metabolites, off-target toxicity, on-target
toxicity, and immune reaction
Celluar Responses to Chemically Induced Toxicity:
* Prof. Christopher Bradfield of the University of Wisconsin will
speak on studies with the AhR receptor and genomic and informatic
approaches to understanding its roles
* Prof. Thomas Kensler of Johns Hopkins University will speak on the
Keap1/Nrf2 system in a model of regulation of pathways by toxicant
reactions
* Dr. S. G. Rhee of NIH will speak on redox linked regulatory
systems, including the peridoxins, and their roles as mediators
of response to toxic injury
* Dr. Donald Nicholson of Merck will discuss the role of apoptosis
in cell injury
Potential Molecular & In Vitro Approaches to the Detection of Cellular
Responses:
* Lois Lehman-McKeeman of BMS will speak on new technologies that
are impacting decisions in discovery toxicology and overall
strategies for new technology applications.
* Tim Ryan of Eli Lilly will present case studies illustrating the
application of genomic technology to safety assessment.
* Cindy Afshari of Amgen will present case studies on combining in
vitro models with new technology in early safety screening, and
safety assessment of bioproducts.
* Don Robertson of Pfizer will present case studies illustrating the
use of metabonomics as an early safety assessment tool.
* Dr. James Stevens of Eli Lilly, a leader in the area of molecular
toxicology, will chair this session.
The Status of Molecular Approaches (Whats Working, Whats Yet to Be Done):
* David Jacobsen-Kramm of the FDA Office of Pharmacology and
Toxicology will speak on the agencys efforts to understand how
to best utilize technologies to predict potential human risk
* Bruce Carr of BMS will speak on identifying signals of potential
concern for human tox in drug candidates
* Michael Cunningham of NIEHS will speak on exploring how effects
of chemicals on various organ systems can be detected with
molecular tools at doses that are not associated with frank toxicity
* Eric Bloome of Abbott will speak on molecular/in vitro approaches
to assessing potential chemical induced toxicity in a drug
development environment.
Keynote:
* Prof. Gilbert Omenn of the University of Michigan and current
President of the American Association for the Advancement of
Science (AAAS) will speak on the promise and challenge of
accurately predicting potential human risk.
Short Course (optional):
* Roger Ulrich of Merck/Rosetta will give an overview of genomics
and small RNA interference, Prof. Daniel Liebler of Vanderbilt
University will give an overview on proteomics and metabolomics.
An FDA perspective is also planned, with the speaker TBD.
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