Fragment-based drug design facilitates selective kinase inhibitor discovery.

Protein kinases (PKs) are important drug targets, but kinases selectivity poses a challenge to protein kinase inhibitors (PKIs) design. Fragment-based drug discovery (FBDD) has achieved great success in the discovery of highly specific PKIs. It makes full use of kinase-fragment interaction in target kinase subpockets to obtain promising selectivity. However, it's difficult to understand the complicated kinase-fragment interaction space, and systemic discussion of these interactions is still lacking. Herein, we introduce the advantages of the FBDD strategy in PKIs design. Key features of the selectivity of kinase-fragment interactions are summarized and analyzed. Some promising PKIs are introduced as case studies to help understand the fragment-to-lead (F2L) optimization process. Novel strategies and technologies for FBDD in PKIs discovery are also outlooked.