Corporate Banner
Satellite Banner
ADME Tox
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Validation of Drug Toxicity Prediction using DiscoveRx Model

Published: Tuesday, May 20, 2014
Last Updated: Tuesday, May 20, 2014
Bookmark and Share
BioMAP® Systems was shown to identify important safety aspects of drugs and chemicals more efficiently and accurately than can be achieved by animal testing.

Data from BioMAP Systems analysis of 776 environmental chemicals, including reference pharmaceuticals and failed drugs, on their ability to disrupt physiologically important human biological pathways were published this week in Nature Biotechnology. The results show that this in vitro approach can reproducibly identify potential toxicities and off-target drug effects, as well as pinpoint cellular mechanisms and specifically affected biomarker endpoints underlying specific types of adverse reactions in humans. DiscoveRx Corporation’s BioSeek division conducted the analysis in collaboration with scientists from the U.S. Food and Drug Administration, National Institutes of Health and U.S. Environmental Protection Agency as part of the EPA ToxCast Program.

Assessing the safety aspects of drugs, consumer products and environmental chemicals has been historically undertaken through animal testing. However, the vast number of chemicals needing such toxicological assessment  and the fact that results in animals often do not translate well to results in humans require the development of alternative, faster, more accurate and humane testing approaches.

“This publication examines an unprecedentedly large data set in terms of number of chemicals, chemical diversity and types of assays screened phenotypically in BioMAP primary human cell models of tissue biology and disease,” said Ellen L. Berg, Ph.D., Scientific Director and General Manager of DiscoveRx’s BioSeek division and an author of the publication.  “In contrast to screening approaches aimed at understanding the actions of a single agent at the molecular and mechanistic level, this method harvests the collective knowledge embedded in reference chemicals with respect to their molecular targets, mechanisms of action, and animal and human toxicity and applies it to characterizing the biological activity of new chemicals or medicines.

“Our results show such systems to be a highly useful and reproducible tool for predictive toxicology that can identify potential chemical targets, toxicological liabilities and molecular mechanisms that elucidate specific adverse outcome pathways for drugs and other chemicals,” Dr. Berg continued. “Even using a limited set of primary human cell systems, we were able to recognize consistent patterns of activity that were closely correlated with diverse drug actions and toxicities. New chemicals falling into profile clusters with known activities suggest specific potential toxicities for more careful evaluation, greatly increasing the efficiency of toxicity testing by focusing resources for follow-up testing on the bioactivities of highest concern.”

For example, drugs and chemicals, including selective estrogen receptor modulators, tamoxifen and raloxifene, that are associated with thrombosis-related side effects, like deep vein thrombosis (DVT), were found to preferentially increase the levels of tissue factor in BioMAP models of vascular inflammation.  Thus, the use of these models for screening earlier in the drug discovery process may help identify new medicines with reduced potential for this debilitating side effect.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,300+ scientific posters on ePosters
  • More than 4,800+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

DiscoveRx Corporation Acquires Bioseek
DiscoveRx adds primary cell assays to its portfolio of drug discovery solutions.
Thursday, November 08, 2012
Scientific News
Colon Cancer Blocked in Mice
Case Western Reserve University Researchers block common type of colon cancer tumour in mice, laying groundwork for human clinical trial.
Protein Nanocages Could Improve Drug Design and Delivery
HHMI scientists have designed and built 10 large protein icosahedra that are similar to viral capsids that carry viral DNA.
Development in Preventing Macular Degeneration
Following macular degeneration insight, promising drugs to prevent vision loss have been identified.
Improving Tumour Therapy with Nanoparticles
UHN nanoparticle called PEARLs is a promising utilisation of photo-thermal therapy for cancer treatment.
New Antidepressant Treatment Discovered
Scientists have demonstrated how gene therapy could lead to new treatments for depression.
Cellular Origin of Skin Cancer Identified
Scientists have identified ‘cell of origin’ in the most common form of skin cancer, and followed the process that leads to tumour growth.
Enhancing Drug Safety with a Web-Based Data Tool
Online and open-access tool allows anyone to find, combine and analyse FDA drug information.
Genetic Missing Link Could Explain Mystery of Heritability
Mother’s diet during pregnancy can permanently affect offspring attributes through process that could be strongly influenced by genetic variation in an unexpected part of the genome.
Does the Transport of Next-Gen Vaccines Lie with E.coli?
Study shows harmless E.coli capsule could aid next-gen vaccine delivery and efficiency.
Breathing in a Cure
Researchers working on inhalable ibuprofen to treat cystic fibrosis.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!