Janus kinase (JakA) family: Introduction

Janus kinases (JAKs) are a family of four enzymes; JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). They are essential for cytokine signalling and are strongly linked to both cancer and inflammatory diseases.

Several non-selective JAK inhibitors (jakinibs) are currently approved for clinical use: tofacitinib and baricitinib for rheumatoid arthritis, and ruxolitinib for myeloproliferative neoplasms. The volume of recent patent literature attests to the continued drug discovery interest in this family of enzymes [2-3], noting the intense interest directed towards exploiting JAK inhibition as a strategy for combating immune and inflammatory diseases [4-5]. JAK1-selective inhibitors are thought to exhibit enhanced utility compared to pan-jakinibs, with examples such as upadacitinib (ABT-494), filgotinib (GLPG0634), itacitinib (INCB-039110) and PF-04965842 already in mid-stage clinical trials. He and Guttman-Yassky published a review of the development of JAK inhibitors for atopic dermatitis in late 2018 [1].

References

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1. He H, Guttman-Yassky E. (2019) JAK Inhibitors for Atopic Dermatitis: An Update. Am J Clin Dermatol, 20 (2): 181-192. [PMID:30536048]

2. Kettle JG, Åstrand A, Catley M, Grimster NP, Nilsson M, Su Q, Woessner R. (2017) Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1. Expert Opin Ther Pat, 27 (2): 127-143. [PMID:27774824]

3. Kettle JG, Åstrand A, Catley M, Grimster NP, Nilsson M, Su Q, Woessner R. (2017) Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 2. Expert Opin Ther Pat, 27 (2): 145-161. [PMID:27774822]

4. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. (2017) JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov, 17 (1): 78. [PMID:29282366]

5. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. (2017) JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov, 16 (12): 843-862. [PMID:29104284]

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Janus kinase (JakA) family, introduction. Last modified on 12/03/2019. Accessed on 14/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/FamilyIntroductionForward?familyId=581.