A new study helps to explain what defines how long a drug molecule stays bound to its target.

When a drug molecule binds to its target protein, it stays bound for some time before eventually unbinding the target. The actual time how long a drug molecule resides bound to its target varies among compounds. The lifetime of the drug-target complex may play a crucial role in drug efficacy, as a long target residence time can, in some cases, be important for drug efficacy. Therefore, understanding its underlying causes enables more rational drug design.

In the new study, researchers from the University of Eastern Finland and the University of Tubingen identified the key elements driving for a long or a short target residence time among similar small molecule kinase inhibitors on the atomistic level. The findings were published in Nature Communications.

Dozens of small molecule kinase inhibitors have already been approved for clinical use, most of them for the treatment of cancer.

«Initially, we were interested in what causes the discrepancy in the target residence time between two similar small molecule kinase inhibitors,» says Senior Researcher, lead author Tatu Pantsar from the University of Eastern Finland.

Prof. Stefan Laufer’s group at the University of Tubingen has designed, synthesized and biologically characterized numerous small molecule kinase inhibitors for a protein kinase called p38a MAPK, which enabled this research.

Story Source: Materials provided by University of Eastern Finland. Note: Content may be edited for style and length.