Prolonged binding results in higher drug efficacy
2021
Goethe University Frankfurt, Frankfurt, Germany
There is increasing evidence that the efficacy of a drug correlates with the residence time of a pharmaceutical substance at its specific binding site. The signalling protein FAK (Focal Adhesion Kinase) plays a role in cancer and inhibition of this kinase induces slowing down breast cancer cells, thus also slowing metastasizing. Analysis of different FAK inhibitors showed that the most effective ones show prolonged residence time at the FAK signalling protein binding site. The binding of effective inhibitors induces a conformational change which explains the prolonged binding. The binding behaviour of the inhibitors can be modelled in computer simulations. The combination of biochemical and molecular biological as well as in silico analyses is a new and promising method for optimizing pharmaceutical active ingredients in the future.
Structure-kinetic relationship reveals the mechanism of selectivity of FAK inhibitors over PYK2
Stefan Knapp
Added on: 03-11-2022
[1] www.cell.com/cell-chemical-biology/fulltext/S2451-9456(21)00003-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451945621000039%3Fshowall%3Dtrue[2] https://www.bionity.com/en/news/1169629/pharmaceutical-research-when-active-substance-and-target-protein-embrace-each-other.html
