An Innovative High-Throughput Screening Approach for Discovery of Small Molecules That Inhibit TNF Receptors.

ABSTRACT: Tumor necrosis factor receptor 1 (TNFR1) is a transmembrane receptor that binds tumor necrosis factor or lymphotoxin-alpha and plays a critical role in regulating the inflammatory response. Upregulation of these ligands is associated with inflammatory and autoimmune diseases. Current treatments reduce symptoms by sequestering free ligands, but this can cause adverse side effects by unintentionally inhibiting ligand binding to off-target receptors. Hence, there is a need for new small molecules that specifically target the receptors, rather than the ligands. Here, we developed a TNFR1 FRET biosensor expressed in living cells to screen compounds from the NIH Clinical Collection. We used an innovative high-throughput fluorescence lifetime screening platform that has exquisite spatial and temp

SUBMITTER: Lo CH 

PROVIDER: S-EPMC5899890 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature