Identification
and Mitigation of Reactive Metabolites
of 2‑Aminoimidazole-Containing Microsomal Prostaglandin E Synthase‑1
Inhibitors Terminated Due to Clinical Drug-Induced Liver Injury
Version 2 2018-02-22, 21:03
Version 1 2018-02-15, 18:03
Posted on 2018-02-22 - 21:03
Two 2-aminoimidazole-based
inhibitors, LY3031207 (1) and LY3023703 (2), of the microsomal prostaglandin
E synthase-1 (mPGES-1) enzyme were found to cause drug-induced liver
injury (DILI) in humans. We studied imidazole ring substitutions to
successfully mitigate reactive metabolite (RM) formation. These studies
support the conclusion that RM formation may play a role in the observations
of DILI and the consideration of 2-aminoimidazoles as structure alerts,
due to the high likelihood of bioactivation to generate RMs.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Norman, Bryan H.; Fisher, Matthew J.; Schiffler, Matthew A.; Kuklish, Steven L.; Hughes, Norman E.; Czeskis, Boris A.; et al. (2018). Identification
and Mitigation of Reactive Metabolites
of 2‑Aminoimidazole-Containing Microsomal Prostaglandin E Synthase‑1
Inhibitors Terminated Due to Clinical Drug-Induced Liver Injury. ACS Publications. Collection. https://doi.org/10.1021/acs.jmedchem.7b01806
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
AUTHORS (10)
BN
Bryan H. Norman
MF
Matthew J. Fisher
MS
Matthew A. Schiffler
SK
Steven L. Kuklish
NH
Norman E. Hughes
BC
Boris A. Czeskis
KC
Kenneth C. Cassidy
TA
Trent L. Abraham
JA
Jeffrey J. Alberts
DL
Debra Luffer-Atlas