March 23, 2024eLifeOpen Access

Impact of the clinically approved BTK inhibitors on the conformation of full-length BTK and analysis of the development of BTK resistance mutations in chronic lymphocytic leukemia

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Authors

RJR JosephIowa State University TWThomas E. WalesNortheastern University SJSandrine JayneUniversity of Leicester

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Implication

Structural analysis demonstrates that five approved BTK inhibitors induce distinct conformational shifts in full-length BTK, explaining drug-specific resistance mutations in leukemia.

Key Points

Approved BTK inhibitors induce distinct allosteric changes in full-length Bruton's tyrosine kinase, shifting the protein's overall conformational equilibrium.
Structural responses diverge across five approved drugs including ibrutinib and pirtobrutinib, explaining resistance mutations such as BTK T474I and L528W.
Analysis of covalent and reversible kinase active site inhibitors highlights allosteric mechanisms governing drug-specific resistance in chronic lymphocytic leukemia.

Cite This Study

Joseph et al. (2024) studied this question.

synapsesocial.com/papers/68e72a7db6db6435876a4770 https://doi.org/10.7554/elife.95488

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Implication

Structural analysis demonstrates that five approved BTK inhibitors induce distinct conformational shifts in full-length BTK, explaining drug-specific resistance mutations in leukemia.

Impact of the clinically approved BTK inhibitors on the conformation of full-length BTK and analysis of the development of BTK resistance mutations in chronic lymphocytic leukemia

Discussion

Member takes

Implication

Key Points

Cite This Study

Impact of the clinically approved BTK inhibitors on the conformation of full-length BTK and analysis of the development of BTK resistance mutations in chronic lymphocytic leukemia

Discussion

Member takes

Implication

Key Points

Cite This Study

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