Discovery of quinoline-based irreversible BTK inhibitors.

Bioorganic & Medicinal Chemistry Letters
Gerjan de BruinTjeerd Barf

Abstract

Bruton tyrosine kinase (BTK) is an important target in oncology and (auto)immunity. Various BTK inhibitors have been approved or are currently in clinical development. A novel BTK inhibitor series was developed starting with a quinazoline core. Moving from a quinazoline to a quinoline core provided a handle for selectivity for BTK over EGFR and resulted in the identification of potent and selective BTK inhibitors with good potency in human whole blood assay. Furthermore, proof of concept of this series for BTK inhibition was shown in an in vivo mouse model using one of the compounds identified.

Citations

Mar 20, 2021·European Journal of Medicinal Chemistry·Jiakuo LiuTiantai Zhang
May 26, 2021·Journal of Biomolecular Structure & Dynamics·Anju AnjuAnil Kumar Mishra

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.