scholarly journals Physical and functional characterization of the genetic locus of IBtk, an inhibitor of Bruton's tyrosine kinase: evidence for three protein isoforms of IBtk

2008 ◽  
Vol 36 (13) ◽  
pp. 4402-4416 ◽  
Author(s):  
Carmen Spatuzza ◽  
Marco Schiavone ◽  
Emanuela Di Salle ◽  
Elzbieta Janda ◽  
Marco Sardiello ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Genetic Locus ◽  
Functional Characterization ◽  
Protein Isoforms ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase

Characterization of novel Bruton's tyrosine kinase gene mutations in Central European patients with agammaglobulinemia

2007 ◽  
Vol 44 (7) ◽  
pp. 1639-1643 ◽  
Author(s):  
Doris Kristufek ◽  
Rosa Maria Aspalter ◽  
Martha Marianne Eibl ◽  
Hermann Maximilian Wolf
Keyword(s):  
Tyrosine Kinase ◽  
Gene Mutations ◽  
Bruton’S Tyrosine Kinase ◽  
Kinase Gene ◽  
Bruton's Tyrosine Kinase ◽  
Central European ◽  
Tyrosine Kinase Gene

scholarly journals Characterization of Bruton’s Tyrosine Kinase Gene and Protein from Marine Sponge Suberites domuncula

2012 ◽  
Vol 85 (2) ◽  
pp. 223-229 ◽  
Author(s):  
Drago Perina ◽  
Andreja Mikoč ◽  
Matija Harcet ◽  
Mirna Imešek ◽  
Dujo Sladojević ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Marine Sponge ◽  
Bruton’S Tyrosine Kinase ◽  
Kinase Gene ◽  
Bruton's Tyrosine Kinase ◽  
Suberites Domuncula ◽  
Tyrosine Kinase Gene

Characterization of Bruton's tyrosine kinase mutations in Mexican patients with X-linked agammaglobulinemia

2008 ◽  
Vol 45 (4) ◽  
pp. 1094-1098 ◽  
Author(s):  
G. Lopez-Herrera ◽  
L. Berron-Ruiz ◽  
D. Mogica-Martinez ◽  
F. Espinosa-Rosales ◽  
L. Santos-Argumedo
Keyword(s):  
Tyrosine Kinase ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Mexican Patients

scholarly journals Merits and Pitfalls in the Characterization of Covalent Inhibitors of Bruton’s Tyrosine Kinase

2018 ◽  
Vol 23 (10) ◽  
pp. 1040-1050
Author(s):  
Christopher M. Harris ◽  
Sage E. Foley ◽  
Eric R. Goedken ◽  
Mark Michalak ◽  
Sara Murdock ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Recovery Of Function ◽  
Quantitative Description ◽  
Cellular Level ◽  
Time Dependent ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Covalent Inhibitors

In vitro analysis of covalent inhibitors requires special consideration, due to the time-dependent and typically irreversible nature of their target interaction. While many analyses are reported for the characterization of a final candidate, it is less clear which are most useful in the lead optimization phase of drug discovery. In the context of identifying covalent inhibitors of Bruton’s tyrosine kinase (BTK), we evaluated multiple techniques for characterizing covalent inhibitors. Several methods qualitatively support the covalent mechanism of action or support a particular aspect of interaction but were not otherwise informative to differentiate inhibitors. These include the time dependence of IC50, substrate competition, mass spectrometry, and recovery of function after inhibitor removal at the biochemical and cellular level. A change in IC50 upon mutation of the targeted BTK C481 nucleophile or upon removal of the electrophilic moiety of the inhibitor was not always a reliable indicator of covalent inhibition. Determination of kinact and KI provides a quantitative description of covalent interactions but was challenging at scale and frequently failed to provide more than the ratio of the two values, kinact/KI. Overall, a combination of approaches is required to assess time-dependent, covalent, and irreversible inhibitors in a manner suitable to reliably advance drug candidates.

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