Related Experiment Video
Updated: Apr 7, 2026

Vasodilation of Isolated Vessels and the Isolation of the Extracellular Matrix of Tight-skin Mice
Published on: March 24, 2017
Structure-Based Development of a Protein-Protein Interaction Inhibitor Targeting Tumor Necrosis Factor
Jun Moriya1, Koh Takeuchi2, Kenji Tai1
1†Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai 5-1-3, Tsukuba-shi, Ibaraki 300-2635, Japan.
Abstract:
The interactions between tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and TNF superfamily receptors (TNFRSFs) are promising targets for rheumatoid arthritis (RA) treatment. However, due to the challenging nature of protein-protein interactions (PPIs), a potent inhibitor that surpasses the affinity of the TRAF6-TNFRSF interactions has not been developed. We developed a small-molecule PPI inhibitor of TRAF6-TNFRSF interactions using NMR and in silico techniques. The most potent compound, TRI4, exhibited an affinity higher than those of TNFRSFs and competitively inhibited a TRAF6-TNFRSF interaction. Structural characterization of the TRAF6-TRI4 complex revealed that TRI4 supplants key interactions in the TRAF6-TNFRSF interfaces. In addition, some TRAF6-TRI4 interactions extend beyond the TRAF6-TNFRSF interfaces and increase the binding affinity. Our successful development of TRI4 provides a new opportunity for RA treatment and implications for structure-guided development of PPI inhibitors.
More Related Videos
05:08Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
Published on: July 8, 2025
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
Related Concept Videos
Protein-protein Interfaces
Protein Networks
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Targeted Cancer Therapies
There are several types of targeted therapies against...
Targets for Drug Action: Overview
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...