Exploring the natural chemiome to target interleukin-6 receptor (IL-6R) cytokines: an atomic scale investigation for novel rheumatoid arthritis drug discovery
AUTOR(ES)
Chen, Qiujian, Niu, Xiaohui, Li, Nana
FONTE
Braz. J. Pharm. Sci.
DATA DE PUBLICAÇÃO
01/02/2018
RESUMO
ABSTRACT Natural compounds are a gold mine for treating rheumatoid arthritis (RA). The etiology of this disease is linked to inflammation, where cytokines play an important role. Strategies have been drafted for targeting cytokines as a therapeutic option in patients with RA. Inhibiting cytokines with natural compounds has become a major focus for the development of drugs to treat RA. Here, a structure-based drug design approach was employed to identify novel leads to target the interleukin 6 receptor (IL-6R). A total of 48,531 compounds of natural origin were screened. Two of these compounds were shortlisted for molecular docking simulation and tested for inhibiting gp130 dimerization in human macrophages. The results show that Lead5 (CID5329098) significantly inhibited the release of gp130 in a dose-dependent manner, similar to the inhibitory effect of LMT-28 (p<0.005). This study provides an atomic scale outcome of a single natural compound that can be developed into a RA drug.
Documentos Relacionados
- Detection of Direct Binding of Human Herpesvirus 8-Encoded Interleukin-6 (vIL-6) to both gp130 and IL-6 Receptor (IL-6R) and Identification of Amino Acid Residues of vIL-6 Important for IL-6R-Dependent and -Independent Signaling
- Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis.
- The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.
- Circadian rhythm of serum interleukin-6 in rheumatoid arthritis.
- Effect of cyclosporin A on interleukin-6 and soluble interleukin-2 receptor in patients with rheumatoid arthritis.