Toll-like Receptor 4 Small Molecule Modulators

doi:10.11944/j.issn.1000-0518.2016.08.160206

Chinese Journal of Applied Chemistry ›› 2016, Vol. 33 ›› Issue (8): 876-886.DOI: 10.11944/j.issn.1000-0518.2016.08.160206

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Toll-like Receptor 4 Small Molecule Modulators

ZHANG Xiaozheng^a^b^c,ZHANG Tianshu^a,CUI Fengchao^d,LI Yunqi^d,PENG Yinghua^e,WANG Xiaohui^a^c^*()

^a Chemical Biology Laboratory,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China
^b University of Chinese Academy of Sciences,Beijing 100039,China
^c State Key Laboratory of New Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China
^d Key Laboratory of Synthetic Rubber,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China
^e Key Laboratory of Special Animal Molecular Biology of Jilin Province,Specialty Research Institute of Chinese Academy of Agricultural Sciences,Changchun 130022,China

Received:2016-05-18 Accepted:2016-06-06 Published:2016-07-21 Online:2016-07-21
Contact: WANG Xiaohui
Supported by:
Supported by National Natural Science Foundation of China(No.21543013), Open Fund of State Key Laboratory of New Drugs, Shanghai Institute of Materia Medica, Chinese Academy of Sciences(No.SIMM1601KF-17), Natural Science Foundation of Jilin Province(No.20160101211JC), Foundation for Returned Overseas Chinese Scholars of Jilin Province, Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fund (the second phase)

Abstract

Abstract:

Toll-like receptors(TLRs) are evolutionarily conserved innate immunity receptor proteins that detect pathogen-associated molecular patterns(PAMPs), danger-associated molecular patterns(DAMPs) and xenobiotic-associated molecular patterns(XAMPs), triggering inflammatory responses. TLR4 is the main receptor for bacterial lipopolysaccharide(LPS) and the accessory protein myeloid differentiation factor 2(MD-2) is responsible for ligand recognition. LPS binding induces(TLR4-MD-2-LPS)2 and TLR4/MD-2 complex dimeriztion, which activates TLR4 signaling and produce pro-inflammatory factors. The dysregulation of innate immune TLR4 signaling contributes to numerous pathological diseases. Therefore, TLR4/MD-2 is emerging as an important drug discovery target. In this review, we summarize the up-to-date discovery of TLR4 small molecule modulators and provide insights into future drug discovery, which will be interesting to colleagues major in chemical biology, medicinal chemistry, signal transduction and translational medicine.

Key words: Toll-like receptor 4, myeloid differentiation factor 2, drug discovery, agonist, antagonist, innate immune

ZHANG Xiaozheng,ZHANG Tianshu,CUI Fengchao,LI Yunqi,PENG Yinghua,WANG Xiaohui. Toll-like Receptor 4 Small Molecule Modulators[J]. Chinese Journal of Applied Chemistry, 2016, 33(8): 876-886.

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Toll-like Receptor 4 Small Molecule Modulators

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