doi.org/10.1016/j.bmc.2019.115236

What is it about?

Bruton's tyrosine kinase (BTK) and Janus kinase 3 (JAK3) are very promising targets for hematological malig- nancies and autoimmune diseases. In recent years, a few compounds have been approved as a marketed medicine, and several are undergoing clinical trials. By recombining the dominant backbone of known active compounds, constructing a foused library, and screening a broad panel of kinases, we found a class of com- pounds with dual activities of anti-BTK and anti-JAK3. Some of the compounds have shown 10-folds more active in the enzyme and cell-based assays than a known active compound. Furthermore, liver microsome stability experiments show that these compounds have better stability than ibrutinib. These explorations offered new clues to discover benzoxaborole fragment and pyrimidine scaffold as more effective BTK and JAK3 dual in-hibitors.

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Photo by Raphaël Biscaldi on Unsplash

Photo by Raphaël Biscaldi on Unsplash

Why is it important?

Highlights  A dominant pharmacophore re-combination strategy was successfully used to design kinases inhibitors.  A series of boron-containing compounds were synthesized, and some of them exhibited significant inhibitory activity against BTK and JAK3 with both IC50 values below 1 nM.  Several compounds have shown 10-folds more active in the enzyme and cell-based assays than a known active compound, ibrutinib and CC292. The diversity of atoms in drug molecules has been expanded

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