LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Discovery of Cysteine-targeting Covalent Protein Kinase Inhibitors.

Photo from wikipedia

Small molecule covalent kinase inhibitors (CKIs) have entered a new era in drug discovery, which have the advantage for sustained target inhibition and high selectivity. An increased understanding of binding… Click to show full abstract

Small molecule covalent kinase inhibitors (CKIs) have entered a new era in drug discovery, which have the advantage for sustained target inhibition and high selectivity. An increased understanding of binding kinetics of CKIs and discovery of additional irreversible and reversible-covalent cysteine-targeted warheads has inspired the development of this area. Herein, we summarize the major medicinal chemistry strategies employed in the discovery of these representative CKIs, which are categorized by the location of the target cysteine within seven main regions of the kinase: the front region, the glycine rich loop (P-loop), the hinge region, the DFG region, the activation loop (A-loop), the catalytic loop (C-loop), and the remote loop. The emphasis is placed on the design and optimization strategies of CKIs that are generated by addition of a warhead to a reversible lead/inhibitor scaffold. In addition, we address the challenges facing this area of drug discovery.

Keywords: chemistry; kinase inhibitors; loop loop; cysteine

Journal Title: Journal of medicinal chemistry
Year Published: 2021

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.