Greek researchers have found two molecules — T23 and T8 — that show promise in treating rheumatoid arthritis and other chronic inflammatory diseases. Both molecules act against tumor necrosis factor (TNF) and the receptor activator of NF-κB ligand (RANKL).
Their study, “Cheminformatics-aided discovery of small-molecule Protein-Protein Interaction (PPI) dual inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL)” appeared in the journal PLoS Computational Biology.
Abnormally high levels of TNF cause the inflammation seen in rheumatoid arthritis, Crohn’s disease, psoriasis and other diseases. RANKL, a protein, is also thought to play a role in causing inflammation. Many drugs on the market target TNF, but not all patients respond to them, and some of these drugs lose their effectiveness over time or cause serious side effects.
Researchers used advanced computer technology to analyze the structure of nearly 15,000 small molecules to predict whether they interact with TNF and RANKL, and how well they might disrupt their pro-inflammatory activity. T23 and T8 were among the nine molecules found.
“This virtual experiment identified nine promising molecules out of thousands of candidates,” Antreas Afantitis, the study’s co-author, said in a press release.
Researchers found that T23 and T8 were strong TNF inhibitors. They also studied the two molecules’ potential toxicity and found it to be low.
“Using a combination of an in silico drug discovery pipeline…and in vitro experiments, we identified compounds T8 and T23 as dual inhibitors of TNF and RANKL,” the team concluded. “These compounds present low toxicity and may be further optimized in drug design targeting TNF and RANKL to develop improved treatments for a range of inflammatory and autoimmune diseases.”