Selective JAK1 inhibitors and the therapeutic applications thereof: a patent review (2016-2023)

The family of Janus kinases (JAKs) consists of four intracellular non-receptor tyrosine kinases: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). Among these four subtypes, JAK1 is the only isoform that can form heterodimers with all three JAKs, and JAK1 dysfunction can lead to inflammation and severe autoimmune diseases. Interest in JAK1 inhibitors has grown tremendously, and the number of inhibitors targeting JAK1 continues to rise annually.

This paper reviews JAK1 small molecule inhibitors that were reported in patent literature from January 2016 to December 2023. Web of Science, SciFinder, PubMed, WIPO, EPO, USPTO, and CNIPA databases were used for searching the literature and patents for JAK1 inhibitors.

JAK1 inhibitors show great promise in treating cytokine dysregulated disorders; nevertheless, nonselective JAK1 inhibitors have more severe side effects, which restricts the therapy's safety and use. Therefore, developing highly selective JAK1 inhibitors can mitigate potential risks and lead to next-generation therapies with improved efficacy and safety profiles.