New Computational Tool for Treatment

Many human tumours express indoleamine 2,3-dioxygenase (IDO), an enzyme which mediates an immune-escape in several cancer types. Researchers developed an approach for creating new IDO inhibitors by computer-assisted structure-based drug design.

The docking algorithm used for this project was developed by scientists over the last eight years. It provides solutions for the "lock-and-key" problem, wherein the protein active site is regarded as a "lock", which can be fitted with a "key" (usually a small organic molecule) able to regulate its activity. Once an interesting molecule has been obtained, synthesis and laboratory experiments are necessary to confirm or reject the prediction. This algorithm will soon be made available to the scientific community worldwide.

The scientists obtained a high success rate. Fifty percent of the molecules designed in silico were active IDO inhibitors in vitro. Compounds that displayed activities in the low micro molar to nano molar range, made them suitable for further testing in tumour cell experiments and for in vivo evaluation in mice. If these studies are successful, scientists can begin evaluating these new compounds in patients undergoing cancer-immunotherapy.

According to the researchers, "This is a satisfactory proof of principle showing that computational techniques can produce very effective inhibitors for specific cancer targets with high yield. This is very encouraging for future drug developments in the academic environment."; Source: Ludwig Institute for Cancer Research