Morichika Takita
   Department   School of Medicine, School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Drug Targeting Based on a New Concept-Targeting Against TLR4 as an Example.
Journal Formal name:Endocrine, metabolic & immune disorders drug targets
Abbreviation:Endocr Metab Immune Disord Drug Targets
ISSN code:18715303/22123873
Volume, Issue, Page 15(2),pp.83-87
Author and coauthor Maru Yoshiro, Tomita Takeshi*, Deguchi Atsuko, Ieguchi Katsuaki, Takita Morichika, Tsukahara Fujiko, Takemura Kazuhiro, Kitao Akio, Gusovsky Fabian
Publication date 2015
Summary TLRs are very important players to regulate innate immune responses. TLR4 controls the host defense by sensing an exotic pathogen, such as lipopolysaccharides. At the same time, some endogenous proteins, including HMGB1 and S100A8, could also function to be a ligand to elicit inflammatory reactions. These facts make TLR4 signaling system very complicated. For instance, the application of TLR4 ligands in cancer therapies is desirable for enhancement of anti-tumor immunity in terms of its reparative nature, but undesirable for enhancement of metastatic growth of cancer cells. In this manuscript, in order to make a novel molecular design to disrupt an interaction between TLR4/MD-2 and endogenous ligands, we provide a potential binding style of the TLR4/MD-2 complex with HMGB1 by using their 3D structural data and docking simulations, and also discuss S100A8 binding to TLR4/MD-2.
DOI 10.2174/187153031502150522123746
PMID 26004773