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)

Georgia Melagraki, Georgios Leonis, Evangelos Ntougkos, Vagelis Rinotas, Christos Papaneophytou, Thomas Mavromoustakos, George Kontopidis, Eleni Douni, George Kollias, Antreas Afantitis

Research output: Contribution to journalReview article

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)661-673
Number of pages13
JournalCurrent Topics in Medicinal Chemistry
Volume18
Issue number8
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Disease
  • Metastasis
  • Osteoprotegerin (OPG)
  • Postmenopausal osteoporosis
  • Rheumatoid arthritis
  • Tumor necrosis factor (TNF)

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