Dual Targeting of Janus Kinase and Bruton’s Tyrosine Kinase: A New Approach to Control the Pathogenesis of Rheumatoid Arthritis
Dual Targeting of Janus Kinase and Bruton’s Tyrosine Kinase: A New Approach to Control the Pathogenesis of Rheumatoid Arthritis
Neelam Pery1*, Fatima Ijaz1, Nayab Batool Rizvi1, Munawar Ali Munawar1 and Muhammad Imtiaz Shafiq2*
ABSTRACT
Rheumatoid arthritis is an autoimmune disease with prevalence all over the world. Several therapeutics with different modes of action are available to deal with the disease but have failed to produce universal response leaving a large proportion of patients untreated. This is due to complex pathogenesis comprising a network of signaling pathways. By controlling one pathway, the pathogenesis continues through complementary pathways. Janus kinase and bruton’s tyrosine kinase regulates a number of T-cell and B-cell mediated signaling pathways ranging from cytokine expression and antibody production to the bone resorption and cartilage destruction. We propose a dual trap to control this pathogenesis in the form of dual JAK3/BTK inhibitor. Using the computer-aided drug designing techniques, we developed dual JAK3 and BTK inhibitors based on quinoxaline derivatives which show appreciable dual inhibition in enzyme assays. To our knowledge, this is the first-ever report on dual JAK3/BTK inhibitors.
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February 2021
Vol. 53, Iss. 1, Pages 1-400
