Drug Targeting Based on a New Concept-Targeting Against TLR4 as an Example

Title:Drug Targeting Based on a New Concept-Targeting Against TLR4 as an Example

Volume: 15 Issue: 2

Author(s): Yoshiro Maru, Takeshi Tomita, Atsuko Deguchi, Katsuaki Ieguchi, Morichika Takita, Fujiko Tsukahara, Kazuhiro Takemura, Akio Kitao and Fabian Gusovsky

Affiliation:

Keywords: Endogenous ligand, HMGB1, immunity, inflammatory, S100A8, TLR4/MD-2.

Abstract: 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.

Cite this article as:

Maru Yoshiro, Tomita Takeshi, Deguchi Atsuko, Ieguchi Katsuaki, Takita Morichika, Tsukahara Fujiko, Takemura Kazuhiro, Kitao Akio and Gusovsky Fabian, Drug Targeting Based on a New Concept-Targeting Against TLR4 as an Example, Endocrine, Metabolic & Immune Disorders - Drug Targets 2015; 15(2) . https://dx.doi.org/10.2174/187153031502150522123746