glpg0634 and Autoimmune-Diseases

Autoimmune and inflammatory diseases place a huge burden on the healthcare system. Small molecule (SM) therapeutics provide much needed complementary treatment options for these diseases. This digest series highlights the latest progress in the discovery and development of safe and efficacious SMs to treat autoimmune and inflammatory diseases with each part representing a class of SMs, namely: 1) protein kinases; 2) nucleic acid-sensing pathways; and 3) soluble ligands and receptors on cell surfaces. In this first part of the series, the focus is on kinase inhibitors that emerged between 2018 and 2020, and which exhibit increased target and tissue selectivity with the aim of increasing their therapeutic index.

Topics: Animals; Autoimmune Diseases; Dose-Response Relationship, Drug; Humans; Inflammation; Molecular Structure; Protein Kinase Inhibitors; Protein Kinases; Small Molecule Libraries; Structure-Activity Relationship

Filgotinib (Jyseleca

Topics: Antirheumatic Agents; Autoimmune Diseases; Humans; Inflammation; Japan; Protein Kinase Inhibitors; Pyridines; Triazoles

The Janus kinases (JAKs) are a family of intracellular tyrosine kinases that play an essential role in the signaling of numerous cytokines that have been implicated in the pathogenesis of inflammatory diseases. As a consequence, the JAKs have received significant attention in recent years from the pharmaceutical and biotechnology industries as therapeutic targets. Here, we provide a review of the JAK pathways, the structure, function, and activation of the JAK enzymes followed by a detailed look at the JAK inhibitors currently in the clinic or approved for these indications. Finally, a perspective is provided on what the past decade of research with JAK inhibitors for inflammatory indications has taught along with thoughts on what the future may hold in terms of addressing the opportunities and challenges that remain.

Topics: Animals; Anti-Inflammatory Agents; Antirheumatic Agents; Autoimmune Diseases; Clinical Trials as Topic; Cytokines; Humans; Inflammation; Inflammatory Bowel Diseases; Janus Kinases; Piperidines; Protein Conformation; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Signal Transduction