Next Article in Journal
Increased Force Variability Is Associated with Altered Modulation of the Motorneuron Pool Activity in Autism Spectrum Disorder (ASD)
Next Article in Special Issue
Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?
Previous Article in Journal
Nerve Growth Factor Signaling from Membrane Microdomains to the Nucleus: Differential Regulation by Caveolins
Previous Article in Special Issue
Revisiting the Metabolism and Bioactivation of Ketoconazole in Human and Mouse Using Liquid Chromatography–Mass Spectrometry-Based Metabolomics
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(4), 694; doi:10.3390/ijms18040694

In Silico and In Vitro Analysis of Interaction between Ximelagatran and Human Leukocyte Antigen (HLA)-DRB1*07:01

1
Drug Metabolism & Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan
2
Institute of Advanced Biosciences, Tokai University, 4-1-1 Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Rolf Teschke
Received: 20 February 2017 / Revised: 21 March 2017 / Accepted: 21 March 2017 / Published: 24 March 2017
(This article belongs to the Special Issue Molecular Research on Drug Induced Liver Injury)
View Full-Text   |   Download PDF [5311 KB, uploaded 24 March 2017]   |  

Abstract

Idiosyncratic ximelagatran-induced hepatotoxicity has been reported to be associated with human leukocyte antigen (HLA)-DRB1*07:01 and ximelagatran has been reported to inhibit the binding of the ligand peptide to HLA-DRB1*07:01 in vitro. In order to predict the possible interaction modes of ximelagatran with HLA-DR molecules, in silico docking simulations were performed. Molecular dynamics (MD) simulations were also performed to predict the effect of ximelagatran on the binding mode of the ligand peptide to HLA-DRB1*07:01. A series of in silico simulations supported the inhibitory effect of ximelagatran on the binding of the ligand peptide to HLA-DRB1*07:01 in vitro. Furthermore, direct interactions of ximelagatran with HLA-DR molecules were evaluated in vitro, which supported the simulated interaction mode of ximelagatran with HLA-DRB1*07:01. These results indicated that ximelagatran directly interacts with the peptide binding groove of HLA-DRB1*07:01 and competes with the ligand peptide for the binding site, which could alter the immune response and lead to the idiosyncratic ximelagatran-induced hepatotoxicity. View Full-Text
Keywords: ximelagatran; melagatran; HLA (human leukocyte antigen); hepatotoxicity; IDT (idiosyncratic drug toxicity); MD (molecular dynamics) simulation ximelagatran; melagatran; HLA (human leukocyte antigen); hepatotoxicity; IDT (idiosyncratic drug toxicity); MD (molecular dynamics) simulation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Hirasawa, M.; Hagihara, K.; Abe, K.; Ando, O.; Hirayama, N. In Silico and In Vitro Analysis of Interaction between Ximelagatran and Human Leukocyte Antigen (HLA)-DRB1*07:01. Int. J. Mol. Sci. 2017, 18, 694.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top