Comparative QSAR model generation using pyrazole derivatives for screening Janus kinase-1 inhibitors

Asthma is a multitargeted disease. IL-4-JAK-STAT signaling pathway is a promising route for the effective control of the disease. JAK inhibition by small molecules could effectively block the IL-4 signaling pathway. It was established that JAK1 is responsive toward IL-4-mediated signaling process. In the present study, three-dimensional QSAR analyses on a set of pyrazole derivatives against JAK1 and JAK2 enzyme inhibition had been executed. Molecular docking studies were conducted with the target JAK1 using the pyrazole derivative compounds and found out potential intermolecular interactions operating among them. The binding energy of all the derivative compounds with the target JAK1 has calculated and found out their affinity toward the target system. These models have predicted the JAK1 inhibitory activity of some five JAK1 active drugs and 50 structurally similar compounds. These models can, thus, suggestively be recommended for virtual screening of JAK1-selective candidates as a lead for immunomodulatory diseases like asthma.