scholarly journals Coupled Enzyme Activity and Thermal Shift Screening of the Maybridge Rule of 3 Fragment Library Against Trypanosoma brucei Choline Kinase; A Genetically Validated Drug Target

10.5772/52668 ◽  
2013 ◽  
Author(s):  
Louise L. ◽  
Helen Denton ◽  
Terry K.
Keyword(s):  
Enzyme Activity ◽  
Trypanosoma Brucei ◽  
Drug Target ◽  
Choline Kinase ◽  
Fragment Library ◽  
Kinase A ◽  
Thermal Shift

Biochemical characterization of highly active Trypanosoma brucei gambiense glycerol kinase, a promising drug target

2013 ◽  
Vol 154 (1) ◽  
pp. 77-84 ◽  
Author(s):  
E. O. Balogun ◽  
D. K. Inaoka ◽  
T. Shiba ◽  
Y. Kido ◽  
T. Nara ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Drug Target ◽  
Biochemical Characterization ◽  
Glycerol Kinase ◽  
Trypanosoma Brucei Gambiense ◽  
Highly Active ◽  
Kinase A

scholarly journals The Molecular Dynamics of Trypanosoma brucei UDP‐Galactose 4′‐Epimerase: A Drug Target for African Sleeping Sickness

2012 ◽  
Vol 80 (2) ◽  
pp. 173-181 ◽  
Author(s):  
Aaron J. Friedman ◽  
Jacob D. Durrant ◽  
Levi C. T. Pierce ◽  
Thomas J. McCorvie ◽  
David J. Timson ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Trypanosoma Brucei ◽  
Drug Target ◽  
Sleeping Sickness ◽  
African Sleeping Sickness

Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay

Science ◽  
2013 ◽  
Vol 341 (6141) ◽  
pp. 84-87 ◽  
Author(s):  
Daniel Martinez Molina ◽  
Rozbeh Jafari ◽  
Marina Ignatushchenko ◽  
Takahiro Seki ◽  
E. Andreas Larsson ◽  
...  
Keyword(s):  
Drug Target ◽  
Drug Transport ◽  
Drug Binding ◽  
Target Engagement ◽  
Tissue Samples ◽  
Target Proteins ◽  
Thermal Shift Assay ◽  
Cellular Thermal Shift Assay ◽  
Thermal Shift ◽  
In Cells

The efficacy of therapeutics is dependent on a drug binding to its cognate target. Optimization of target engagement by drugs in cells is often challenging, because drug binding cannot be monitored inside cells. We have developed a method for evaluating drug binding to target proteins in cells and tissue samples. This cellular thermal shift assay (CETSA) is based on the biophysical principle of ligand-induced thermal stabilization of target proteins. Using this assay, we validated drug binding for a set of important clinical targets and monitored processes of drug transport and activation, off-target effects and drug resistance in cancer cell lines, as well as drug distribution in tissues. CETSA is likely to become a valuable tool for the validation and optimization of drug target engagement.

Regulation of rat Na+-K+-ATPase activity by PKC is modulated by state of phosphorylation of Ser-943 by PKA

1997 ◽  
Vol 273 (6) ◽  
pp. C1981-C1986 ◽  
Author(s):  
Xian-Jun Cheng ◽  
Jan-Olov Höög ◽  
Angus C. Nairn ◽  
Paul Greengard ◽  
Anita Aperia
Keyword(s):  
Enzyme Activity ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Response To Treatment ◽  
Wild Type ◽  
Wild Type Enzyme ◽  
Present Evidence ◽  
Cos Cells ◽  
Kinase C ◽  
Kinase A

We have previously shown that the rat Na+-K+-ATPase α1-isoform is phosphorylated at Ser-943 by protein kinase A (PKA) and at Ser-23 by protein kinase C (PKC), which in both cases results in inhibition of enzyme activity. We now present evidence that suggests that the phosphorylation of Ser-943 by PKA modulates the response of Na+-K+-ATPase to PKC. Rat Na+-K+-ATPase α1 or a mutant in which Ser-943 was changed to Ala-943 was stably expressed in COS cells. The inhibition of enzyme activity measured in response to treatment with the phorbol ester, phorbol 12,13-dibutyrate (PDBu; 10−6 M), was significantly reduced in the cells expressing the Ala-943 mutant compared with that observed in cells expressing wild-type enzyme. In contrast, for cells expressing Na+-K+-ATPase α1 in which Ser-943 was mutated to Asp-943, the effect of PDBu was slightly enhanced. The PDBu-induced inhibition was not mediated by activation of the adenosine 3′,5′-cyclic monophosphate/PKA system and was not achieved via direct phosphorylation of Ser-943. Sp-5,6-DCl-cBIMPS, a specific PKA activator, increased the phosphorylation of Ser-943, and this was associated with an enhanced response to PDBu. Thus the effect of PKC on rat Na+-K+-ATPase α1 is determined not only by the activity of PKC but also by the state of phosphorylation of Ser-943.

Frequent overexpression of aurora B kinase, a novel drug target, in non–small cell lung carcinoma patients

2006 ◽  
Vol 5 (11) ◽  
pp. 2905-2913 ◽  
Author(s):  
Barbara Vischioni ◽  
Joost J. Oudejans ◽  
Wim Vos ◽  
Jose A. Rodriguez ◽  
Giuseppe Giaccone
Keyword(s):  
Lung Carcinoma ◽  
Drug Target ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Aurora B ◽  
Small Cell Lung ◽  
Aurora B Kinase ◽  
Cell Lung Carcinoma ◽  
Novel Drug ◽  
Kinase A
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