상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

A novel small-molecule inhibitor targeting the IL-6 receptor β subunit, glycoprotein 130

Authors 

S S HongJung Ho ChoiS Y LeeY H ParkK Y ParkJ Y LeeJ KimV GajulapatiJ I GooS SinghK LeeYoung-Kook KimS H ImS H AhnS Rose-JohnT H HeoY Choi

Publisher 

American Association of Immunologists

Issue Date 

2015

Citation 

Journal of Immunology, vol. 195, no. 1, pp. 237-245

Abstract 

IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identifiedLMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6-stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6-dependent TF-1 cell proliferation. LMT-28 antagonized IL-6-induced TNF-α production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6Rα, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6Rα complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.

ISSN 

0022-1767

Link 

http://dx.doi.org/10.4049/jimmunol.1402908

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)