학술논문
Correspondence on "Synergy and Antagonism between Allosteric and Active‐Site Inhibitors of Abl Tyrosine Kinase"**.
Document Type
Article
Author
Source
Subject
*PROTEIN-tyrosine kinase inhibitors
*CHRONIC myeloid leukemia
*ISOTHERMAL titration calorimetry
*NUCLEAR magnetic resonance
*ADENOSINE triphosphate
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Language
ISSN
0044-8249
Abstract
Soellner published on the interplay between allosteric and adenosine triphosphate (ATP)‐competitive inhibitors of ABL kinase, showing that the latter preferably binds to different conformational states of ABL compared to allosteric agents that specifically target the ABL myristate pocket (STAMP) and deducing that asciminib cannot bind to ABL simultaneously with ATP‐competitive drugs. These results are to some extent in line with ours, although our analyses of dose‐response matrices from combinations of asciminib with imatinib, nilotinib or dasatinib, show neither synergy nor antagonism, but suggest additive antiproliferative effects on BCR‐ABL‐dependent KCL22 cells. Furthermore, our X‐ray crystallographic, solution nuclear magnetic resonance (NMR), and isothermal titration calorimetry studies show that asciminib can bind ABL concomitantly with type‐1 or ‐2 ATP‐competitive inhibitors to form ternary complexes. [ABSTRACT FROM AUTHOR]