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Specification of Novel Compound E121's Mechanism of Action
Author(s) -
Drummond Shelika,
Manzoor Mohammed,
Cramer Amanda,
Edafiogho Ivan,
Soldato Doreen
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.716.5
Subject(s) - glucocorticoid receptor , glucocorticoid , dexamethasone , antiglucocorticoid , cytokine , pharmacology , receptor , lipopolysaccharide , signal transduction , mechanism of action , suppressor of cytokine signaling 1 , chemistry , western blot , antagonist , endocrinology , medicine , immunology , biology , suppressor , biochemistry , gene , in vitro
Prior research has shown E121, a novel enaminone compound has immunosuppressive ability and potential as a novel therapeutic drug for inflammatory diseases. E121 has shown significant reduction of TNF‐α and IL‐6 and based on its chemical structure, is suggested to act as a glucocorticoid. The aim of this research project is to further elucidate the biochemical signaling pathway through which E121 conducts its effects. By blocking the E121's possible glucocorticoid receptor with RU‐486, it is hypothesized that E121's immunosuppressive ability will be inhibited. This response was compared with that of dexamethasone (a common glucocorticoid) as a control. In this study, lipopolysaccharide (LPS) stimulated mouse macrophages were treated in different conditions with E121, RU‐486 and dexamethasone. From previous research efforts, E121 has exerted an anti‐inflammatory effect by inducing SOCS1 (Suppressor of Cytokine Signaling). Western Blot of LPS stimulated macrophages in the presence and absence of E121 revealed that higher levels of SOCS1 protein were detected in samples containing increasing amounts of E121. Therefore, E121 appears to induce SOCS1. Preliminary research using RU‐486 as a glucocorticoid receptor antagonist also shows that E121 may require the glucocorticoid receptor. Based on its structure, it may resemble the four ring structure of a glucocorticoid and present a novel therapy for autoimmune diseases as an alternative to steroids.