Small-Molecule Inhibitors of Bruton’s Tyrosine Kinase

2017 ◽  
pp. 75-104
Author(s):  
Yingying Zuo ◽  
Zhengying Pan
Keyword(s):  
Tyrosine Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase

scholarly journals Bruton’s Tyrosine Kinase Small Molecule Inhibitors Induce a Distinct Pancreatic Toxicity in Rats

2016 ◽  
Vol 360 (1) ◽  
pp. 226-238 ◽  
Author(s):  
Rebecca I. Erickson ◽  
Leah K. Schutt ◽  
Jacqueline M. Tarrant ◽  
Michelle McDowell ◽  
Lichuan Liu ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Pancreatic Toxicity

scholarly journals Disrupting enzyme fluidity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Ganesh Srinivasan Anand
Keyword(s):  
Mass Spectrometry ◽  
Tyrosine Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
X Ray ◽  
X Ray Crystallography

A combination of X-ray crystallography, NMR, and mass spectrometry has revealed how diverse small-molecule inhibitors bind Bruton’s tyrosine kinase and alter the conformation of this enzyme.

scholarly journals A Small Molecule Inhibitor of Bruton’s Tyrosine Kinase Involved in B-Cell Signaling

ACS Omega ◽  
2017 ◽  
Vol 2 (8) ◽  
pp. 4398-4410 ◽  
Author(s):  
Einav Ratzon ◽  
Itai Bloch ◽  
Meshel Nicola ◽  
Elad Cohen ◽  
Nili Ruimi ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Signaling ◽  
B Cell ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
B Cell Signaling ◽  
Molecule Inhibitor

scholarly journals Fragment-Based Discovery of a Small Molecule Inhibitor of Bruton’s Tyrosine Kinase

2015 ◽  
Vol 58 (14) ◽  
pp. 5437-5444 ◽  
Author(s):  
Christopher R. Smith ◽  
Douglas R. Dougan ◽  
Mallareddy Komandla ◽  
Toufike Kanouni ◽  
Beverly Knight ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Molecule Inhibitor

scholarly journals Pancreatic Effects of a Bruton’s Tyrosine Kinase Small-molecule Inhibitor in Rats Are Strain-dependent

2018 ◽  
Vol 46 (4) ◽  
pp. 460-472 ◽  
Author(s):  
Manoj Bhaskaran ◽  
Paul D. Cornwell ◽  
Steven D. Sorden ◽  
Michael R. Elwell ◽  
Natalie R. Russell ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Small Molecule ◽  
Strain Differences ◽  
Male Rats ◽  
Repeat Dose ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Molecule Inhibitor ◽  
Rat Strain ◽  
Strain Dependent

Inhibitors of Bruton’s tyrosine kinase (BTK) are under development as potential therapies for various autoimmune diseases. In repeat-dose toxicity studies, small-molecule BTK inhibitors (BTKi) have been reported to cause a constellation of histologic effects at the pancreatic endocrine–exocrine interface in male rats; however, similar findings were not reported in other species. Since the BTKi-induced pancreatic effect is morphologically similar to well-documented spontaneous changes (predominantly characterized by insular/peri-insular hemorrhage, pigment deposition, chronic inflammation, and fibrosis) that are known to vary by rat strain, we investigated potential strain-dependent differences in the pancreatic effects of a small-molecule BTKi, LY3337641. Following 13 weeks of LY3337641 treatment, Crl:CD(SD) rats were most sensitive, Crl:WI(Han) rats were of intermediate sensitivity, and Hsd:SD rats were least sensitive. These strain differences appear to be related to differences in rate of weight gain across strains and sexes; however, a definitive mechanism was not determined. This study demonstrated that BTKi-induced pancreatic effects were highly dependent on rat strain and correlated with differences in the incidence and severity of the spontaneous background change. When considered with the lack of pancreas effects in nonrat species, these changes in rats are unlikely predictive of similar changes in humans administered a BTK inhibitor.

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