Discovery of anOrally Active Small-Molecule TumorNecrosis Factor‑α Inhibitor
2020
Tumor
necrosis factor α (TNF-α) is an important therapeutic
target for rheumatoid arthritis, inflammatory bowel disease, and septic
hepatitis. In this study, structure-based virtual ligand screening
combined with in vitro and in vivo assays were applied. A lead compound,
benpyrine, could directly bind to TNF-α and block TNF-α-trigged
signaling activation. Furthermore, the endotoxemic murine model showed
that benpyrine could attenuate TNF-α-induced inflammation, thereby
reducing liver and lung injury. Meanwhile, administration of benpyrine
by gavage significantly relieved the symptoms of collagen-induced
arthritis and imiquimod-induced psoriasiform inflammation in mice.
Thus, our study discovered a novel, highly specific, and orally active
small-molecule TNF-α inhibitor that is potentially useful for
treating TNF-α-mediated inflammatory and autoimmune disease.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI