A Small Molecule Selected from a DNA-Encoded Library of Natural Products That Binds to TNF-α and Attenuates Inflammation In Vivo.

ABSTRACT: Tumor necrosis factor α (TNF-α) inhibitors have shown great success in the treatment of autoimmune diseases. However, to date, approved drugs targeting TNF-α are restricted to biological macromolecules, largely due to the difficulties in using small molecules for pharmaceutical intervention of protein-protein interactions. Herein the power of a natural product-enriched DNA-encoded library (nDEL) is exploited to identify small molecules that interfere with the protein-protein interaction between TNF-α and the cognate receptor. Initially, to select molecules capable of binding to TNF-α , "late-stage" DNA modification method is applied to construct an nDEL library consisted of 400 sterically diverse natural products and pharmaceutically active chemicals. Several natural products, including ka

SUBMITTER: Wang S 

PROVIDER: S-EPMC9313502 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature