Precision targeting of BTK in chronic lymphocytic leukemia: computational insights into structural dynamics and the influence of mutations on BTK inhibitors through QM and MM studies.

Abstract excerpt

Bruton's tyrosine kinase (BTK) is a central mediator of B-cell receptor signaling and a validated therapeutic target in chronic lymphocytic leukemia (CLL). However, the clinical efficacy of both covalent and non-covalent BTK inhibitors is increasingly undermined by resistance-conferring mutations, particularly at residues C481 and T474. These mutations, alone or in combination, pose a significant challenge to...

Topics

• Agammaglobulinaemia Tyrosine Kinase
• Protein Kinase Inhibitors
• Leukemia, Lymphocytic, Chronic, B-Cell
• Molecular Dynamics Simulation