Soluble ligands as drug targets

• Published in: Nature reviews. Drug discovery Vol. 19; no. 10; pp. 695 - 710
• Main Authors: Attwood, Misty M., Jonsson, Jörgen, Rask-Andersen, Mathias, Schiöth, Helgi B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2020; Nature Publishing Group
• Subjects: 631/154/436; 631/154/51; 631/154/51/1568; 631/154/555; 692/699/67; Analysis; Antibodies; Autoimmune Diseases - drug therapy; Autoimmune Diseases - metabolism; Autoimmune Diseases - pathology; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cancer Research; Cytokines; Cytokines - antagonists & inhibitors; Cytokines - metabolism; Drug Design; Drug Discovery; Drugs; Enzymes; Humans; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; Intercellular Signaling Peptides and Proteins - chemistry; Intercellular Signaling Peptides and Proteins - metabolism; Ligands; Medical research; Medicinal Chemistry; Medicine, Experimental; Molecular Medicine; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Pharmaceutical Preparations - metabolism; Pharmacology/Toxicology; Respiratory agents; Review Article; Viral antibodies
• ISSN: 1474-1776; 1474-1784; 1474-1784
• DOI: 10.1038/s41573-020-0078-4

Historically, the main classes of drug targets have been receptors, enzymes, ion channels and transporters. However, owing largely to the rise of antibody-based therapies in the past two decades, soluble protein ligands such as inflammatory cytokines have become an increasingly important class of drug targets. In this Review, we analyse drugs targeting ligands that have reached clinical development at some point since 1992. We identify 291 drugs that target 99 unique ligands, and we discuss trends in the characteristics of the ligands, drugs and indications for which they have been tested. In the last 5 years, the number of ligand-targeting drugs approved by the FDA has doubled to 34, while the number of clinically validated ligand targets has doubled to 22. Cytokines and growth factors are the predominant types of targeted ligands (70%), and inflammation and autoimmune disorders, cancer and ophthalmological diseases are the top therapeutic areas for both approved agents and agents in clinical studies, reflecting the central role of cytokine and/or growth factor pathways in such diseases. With the rise of antibody-based therapies in the past two decades, soluble protein ligands such as inflammatory cytokines have become an increasingly important class of drug targets. This Review analyses drugs targeting ligands that have reached clinical development in the past three decades and discusses strategic issues such as the pros and cons of different ligand-targeting therapeutic modalities.