4 / 8
Volume 4, Issue 2
American Journal of Ethnomedicine
ISSN 2348-9502
Natural Products Congress & World Pharma Congress 2017
October 16-18, 2017
Page 20
Notes:
3
rd
World Congress on
NATURAL PRODUCTS CHEMISTRY AND RESEARCH
&
12
th
WORLD PHARMA CONGRESS
October 16-18, 2017 Budapest, Hungary
Minjun Chen, American Journal of Ethnomedicine, 4:2
DOI: 10.21767/2348-9502-C1-001
The development of liver toxicity knowledge base to support the assessment of drug-induced liver
injury risk in humans
D
rug-Induced Liver Injury (DILI) is a frequent cause of Adverse Drug Reaction (ADR) resulting in clinical trial failure,
warnings and withdrawals of numerous medications. Despite the research community’s best efforts, current testing
strategies aimed at identifying hepatotoxic drugs prior to human trials are not sufficiently powered to predict the complex
mechanisms leading to DILI. Tremendous efforts were conducted to fulfill this knowledge gap. In the FDA’s National Center
for Toxicological Research, we developed the Liver Toxicity Knowledge Base (LTKB), aiming to improve our understanding
and the prediction of DILI risk in humans via integrative analysis of diverse drug-elicited data. In this practice, we discovered
that several drug properties and toxicological properties, such as daily dose, lipophilicity and the capability to form Reactive
Metabolites (RM), are strongly associated with serious DILI potential in humans. Here, we will introduce the rule-of-two
model (i.e. daily dose≥100 mg/day and logP≥3) and DILI score model (i.e. a scoring model derived from daily dose, logP
and formation of RM) developed by the NCTR research team. We will discuss the applications of these models in the context
of regulatory processes with the discussion of independent validations reported in literature. Our studies suggest that these
predictive models (e.g. RO2, DILI score) could help better assess the human DILI risk in drug development process.
Biography
Minjun Chen is a Principal Investigator working at the Division of Bioinformatics and Biostatics of the FDA’s NCTR and serve as the adjunct faculty and mentor for the
bioinformatics program joint by University of Arkansas at Little Rock (UALR) and University of Arkansas for Medical Sciences (UAMS). He received the FDA award for
outstanding junior investigator (2012) and the NCTR scientific achievement award (2014). Currently, he is the Editor together with Yvonne Will (Pfizer) to create a Springer
book titled
Drug-Induced Liver Toxicity.
He also served as the Editorial Board Member for the journals including
Peer J
and
Chinese Herbal Medicine
. He has authored and
co-authored more than 70 book chapters or scientific publications in the prestigious journals. His primary research interests encompass drug-induced liver injury, biomarker
discovery, bioinformatics, and toxicogenomics..
Minjun.Chen@fda.hhs.govMinjun Chen
US Food and Drug Administration, USA