PMID- 26098642
OWN - NLM
STAT- MEDLINE
DCOM- 20160321
LR  - 20181203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 6
DP  - 2015
TI  - The Possible Mechanism of Idiosyncratic Lapatinib-Induced Liver Injury in 
      Patients Carrying Human Leukocyte Antigen-DRB1*07:01.
PG  - e0130928
LID - 10.1371/journal.pone.0130928 [doi]
LID - e0130928
AB  - Idiosyncratic lapatinib-induced liver injury has been reported to be associated 
      with human leukocyte antigen (HLA)-DRB1*07:01. In order to investigate its 
      mechanism, interaction of lapatinib with HLA-DRB1*07:01 and its ligand peptide 
      derived from tetanus toxoid, has been evaluated in vitro. Here we show that 
      lapatinib enhances binding of the ligand peptide to HLA-DRB1*07:01. Furthermore 
      in silico molecular dynamics analysis revealed that lapatinib could change the beta 
      chain helix in the HLA-DRB1*07:01 specifically to form a tightly closed binding 
      groove structure and modify a large part of the binding groove. These results 
      indicate that lapatinib affects the ligand binding to HLA-DRB1*07:01 and 
      idiosyncratic lapatinib-induced liver injury might be triggered by this 
      mechanism. This is the first report showing that the clinically available drug 
      can enhance the binding of ligand peptide to HLA class II molecules in vitro and 
      in silico.
FAU - Hirasawa, Makoto
AU  - Hirasawa M
AD  - Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., 
      Ltd., Tokyo, Japan.
FAU - Hagihara, Katsunobu
AU  - Hagihara K
AD  - Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., 
      Ltd., Tokyo, Japan.
FAU - Okudaira, Noriko
AU  - Okudaira N
AD  - Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., 
      Ltd., Tokyo, Japan.
FAU - Izumi, Takashi
AU  - Izumi T
AD  - Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., 
      Ltd., Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20150622
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (HLA-DRB1*07:01:01 antigen)
RN  - 0 (Quinazolines)
RN  - 0 (Tetanus Toxoid)
RN  - 0VUA21238F (Lapatinib)
SB  - IM
MH  - Chemical and Drug Induced Liver Injury/metabolism/*physiopathology
MH  - HLA-DRB1 Chains/chemistry/*metabolism
MH  - Humans
MH  - Lapatinib
MH  - *Models, Molecular
MH  - Molecular Dynamics Simulation
MH  - Quinazolines/*adverse effects
MH  - Tetanus Toxoid/metabolism
PMC - PMC4476721
COIS- Competing Interests: All authors are employed by Daiichi Sankyo Co., Ltd., but 
      this does not alter the authors' adherence to PLOS ONE policies on sharing data 
      and materials.
EDAT- 2015/06/23 06:00
MHDA- 2016/03/22 06:00
PMCR- 2015/06/22
CRDT- 2015/06/23 06:00
PHST- 2015/03/10 00:00 [received]
PHST- 2015/05/27 00:00 [accepted]
PHST- 2015/06/23 06:00 [entrez]
PHST- 2015/06/23 06:00 [pubmed]
PHST- 2016/03/22 06:00 [medline]
PHST- 2015/06/22 00:00 [pmc-release]
AID - PONE-D-15-10473 [pii]
AID - 10.1371/journal.pone.0130928 [doi]
PST - epublish
SO  - PLoS One. 2015 Jun 22;10(6):e0130928. doi: 10.1371/journal.pone.0130928. 
      eCollection 2015.