Selective JAK1 inhibitor and selective Tyk2 inhibitor patents

• Published in: Expert opinion on therapeutic patents Vol. 22; no. 10; p. 1233
• Main Author: Norman, Peter
• Format: Journal Article
• Language: English
• Published: England 01.10.2012
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - enzymology; Drug Discovery; Humans; Janus Kinase 1 - antagonists & inhibitors; Janus Kinase 1 - metabolism; Molecular Structure; Molecular Targeted Therapy; Multiple Sclerosis - drug therapy; Multiple Sclerosis - enzymology; Patents as Topic; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Structure-Activity Relationship; TYK2 Kinase - antagonists & inhibitors; TYK2 Kinase - metabolism
• ISSN: 1744-7674
• DOI: 10.1517/13543776.2012.723693

The JAK family comprises of the four non-receptor tyrosine kinases JAK1, JAK2, JAK3 and Tyk2, which play key, but differing, roles in cytokine receptor signal transduction. A non-selective JAK inhibitor, ruxolitinib, has recently been approved to treat myelofibrosis whereas tofacitinib is poised for approval to treat rheumatoid arthritis. Selective inhibition of JAK3, JAK1 or Tyk2 provides the opportunity to achieve clinical efficacy in the treatment of inflammatory diseases while reducing the risk of dose-limiting effects attributable to JAK2 inhibition. This review considers the small number of published patent filings that claim either selective JAK1 or selective Tyk2 inhibitors. These are considered in the context of the considerably larger number of disclosures and patent filings claiming selective JAK2 or JAK3 inhibitors. The recent disclosure of the clinical efficacy of a selective JAK1 inhibitor (GLPG-0634) in rheumatoid arthritis and detailed disclosure of the some potent and highly selective JAK1 inhibitors provide a clear stimulus for further activity in this area. The availability of a selective Tyk2 inhibitor will provide the opportunity for better understanding of the physiological role of this kinase. Recent patent applications indicate that Tyk2 selectivity is achievable and Tyk2 inhibitors have potential in the treatment of multiple sclerosis.