A recently developed system-pharmacological model for the dynamics of receptor tyrosine kinases is used to compare di erent targets for drug action: one aiming at binding endogenous ligand needed... Show moreA recently developed system-pharmacological model for the dynamics of receptor tyrosine kinases is used to compare di erent targets for drug action: one aiming at binding endogenous ligand needed for phosphorylation and another binding re- ceptors at their kinase domains and thus preventing them to generate phosphory- lation. We obtain quantitative estimates for the e ectivity of the inhibitor which demonstrate the influence of drug-properties such as dose, a nity to target and drug-elimination rates. Show less
Graaf, P.H. van der; Benson, N.; Peletier, L.A. 2016
Mathematical analysis of pharmacological models is becoming increasingly rel- evant for drug development. Emphasis on mechanistic models has grown and qualitative understanding of complex... Show moreMathematical analysis of pharmacological models is becoming increasingly rel- evant for drug development. Emphasis on mechanistic models has grown and qualitative understanding of complex biological systems has improved a great deal. In this paper we present two examples of basic modular processes which are involved in a wide range of physiological systems. The first model concerns the interaction of a drug with its target, the way the compounds bind and then elicit an effect. The second model is central in signal trans- duction across the cell wall. Both models demonstrate the complex and interesting dynamics which is directly relevant for the impact of the drug. Show less
