Dinitroaniline Interactions with Tubulin: Genetic and Computational Approaches to Define the Mechanisms of Action and Resistance

Author(s):  
Naomi Morrissette ◽  
David Sept
2009 ◽  
Vol 37 (2) ◽  
pp. 333-335 ◽  
Author(s):  
Andrew W. Munro ◽  
Nigel S. Scrutton

Now, more than ever, enzymology and its development can be considered of vital importance to the progression of the biological sciences. With an increase in the numbers of enzymes being identified from genomic studies, enzymology is key to defining the structural and functional properties of these enzymes in order to establish their mechanisms of action and how they fit into metabolic networks. Along with the efforts of the bioinformaticians and systems biologists, such studies will ultimately lead to detailed descriptions of intricate biochemical pathways and allow identification of the most appropriate target enzymes for intervention in disease therapy. Thus the timing for the recent Biochemical Society Focused Meeting entitled ‘Enzyme Mechanisms: Fast Reaction and Computational Approaches’ was highly appropriate. The present paper represents an overview of this meeting, which was held at the Manchester Interdisciplinary Biocentre on 9–10 October 2008.


2015 ◽  
Vol 32 (8) ◽  
pp. 1249-1266 ◽  
Author(s):  
Milla Kibble ◽  
Niina Saarinen ◽  
Jing Tang ◽  
Krister Wennerberg ◽  
Sari Mäkelä ◽  
...  

This article reviews key network pharmacology concepts and recent experimental–computational approaches that have been successfully applied to natural product research, including unbiased elucidation of mechanisms of action and systematic prediction of effective therapeutic combinations.


2003 ◽  
Vol 19 (3) ◽  
pp. 164-174 ◽  
Author(s):  
Stephen N. Haynes ◽  
Andrew E. Williams

Summary: We review the rationale for behavioral clinical case formulations and emphasize the role of the functional analysis in the design of individualized treatments. Standardized treatments may not be optimally effective for clients who have multiple behavior problems. These problems can affect each other in complex ways and each behavior problem can be influenced by multiple, interacting causal variables. The mechanisms of action of standardized treatments may not always address the most important causal variables for a client's behavior problems. The functional analysis integrates judgments about the client's behavior problems, important causal variables, and functional relations among variables. The functional analysis aids treatment decisions by helping the clinician estimate the relative magnitude of effect of each causal variable on the client's behavior problems, so that the most effective treatments can be selected. The parameters of, and issues associated with, a functional analysis and Functional Analytic Clinical Case Models (FACCM) are illustrated with a clinical case. The task of selecting the best treatment for a client is complicated because treatments differ in their level of specificity and have unequally weighted mechanisms of action. Further, a treatment's mechanism of action is often unknown.


Author(s):  
Joe L. Martinez ◽  
Patricia H. Janak ◽  
Susan B. Weinberger ◽  
Gery Schulteis

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
CBS Lau ◽  
VKM Lau ◽  
CL Liu ◽  
PKK Lai ◽  
JCW Tam ◽  
...  

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381 ◽  
Author(s):  
B Ovalle-Magallanes ◽  
A Madariaga-Mazón ◽  
A Navarrete ◽  
R Mata

1979 ◽  
Author(s):  
L Miles ◽  
J Burnier ◽  
M Verlander ◽  
M Goodman ◽  
A Kleiss ◽  
...  

Flu-HPA is one of a series of flufenamic acid derivations that enhances plasminogen-dependent clot lysis in vitro. Studies of possible mechanisms of action of Flu-HPA were undertaken. The influence of Flu-HPA on the inhibition of purified plasmin by purified PI was studied. PI activity was assessed by its inhibition of the clevage of the tripeptide S-2251 (H-D-Val-Leu-Lys-pNA) by plasmin. Flu-HPA was dissolved in DMF or in methonol and preincubated with PI before addition of plasmin. At Flu-HPA concentrations greater than 1mM and up to 60mM, the inhibitory activity of PI was totally lost. The inhibitory effect of normal human plasma on plasmin was also completely abolished at concentrations of Flu-HPA between 2.5 and 40mM. The effect of Flu-HPA on the inhibition of purified plasma kallikrein by purified CI-Inh was also studied. CI-Inh activity was measured by its inhibition of cleavage of the tripeptide Bz-Pro-Phe-Arg-pNA by kallikrein. When Flu-HPA, dissolved in DMF or in methonol, was preincubated with CI-Inh, a concentration dependent inhibition of CI-Inh activity was observed. CI-Inh activity was abolished by concentrations of Flu-HPA greater than 1mM. Flu-HPA also inhibited the activity of CI-Inh on purified Factor XIIa. These observations suggest that this flufenamic acid derivative may enhance fibrinolysis not only by inhibiting PI activity but also by decreasing the inactivation of plasminogen activators by CI-Inh.


Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
D Krüger ◽  
S Wagner ◽  
CW Hann von Weyhern ◽  
F Zeller ◽  
O Kelber ◽  
...  

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