Title:Current Status and Future Prospects of Small–molecule Protein–protein Interaction (PPI) Inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL)
Volume: 18
Issue: 8
Author(s): Georgia Melagraki, Georgios Leonis, Evangelos Ntougkos, Vagelis Rinotas, Christos Papaneophytou, Thomas Mavromoustakos, George Kontopidis, Eleni Douni, George Kollias*Antreas Afantitis*
Affiliation:
- Division of Immunology, Biomedical Sciences Research Center `Alexander Fleming`, Vari,Greece
- Division of Immunology, Biomedical Sciences Research Center `Alexander Fleming`, Vari,Greece
Keywords:
Tumor Necrosis Factor (TNF), osteoprotegerin (OPG), postmenopausal osteoporosis, rheumatoid arthritis, disease,
metastasis.
Abstract: The overexpression of Tumor Necrosis Factor (TNF) is directly related to the development of
several autoimmune diseases, such as rheumatoid and psoriatic arthritis, inflammatory bowel disease,
Crohn's disease, refractory asthma, and multiple sclerosis. Receptor Activator of Nuclear Factor Kappa-
B Ligand (RANKL) belongs to the TNF family and is the primary mediator of osteoclast-induced bone
resorption through interaction with its receptor RANK. The function of RANKL is physiologically inhibited
by the action of osteoprotegerin (OPG), which is a decoy receptor that binds to RANKL and prevents
the process of osteoclastogenesis. Malfunction among RANK/RANKL/OPG can also result in
bone loss diseases, including postmenopausal osteoporosis, rheumatoid arthritis, bone metastasis and
multiple myeloma. To disrupt the unwanted functions of TNF and RANKL, current attempts focus on
blocking TNF and RANKL binding to their receptors. In this review, we present the research efforts
toward the development of low-molecular-weight pharmaceuticals that directly block the detrimental
actions of TNF and RANKL.
