New active substances for activating or inhibiting AGC protein kinases
Dr. Ricardo M. Biondi
Goethe University Frankfurt
Recipient: Goethe University Frankfurt
Funding: GO-Bio Phase I (01.02.2008 - 30.11.2012, 1.814.719 Euro)
Cells employ highly specific enzymes known as protein kinases to regulate themselves and process signals from their environment. If these are defective, it can result in a broad range of ailments. Some forms of cancer and diabetes, for example, are associated with a disruption of protein kinases. Ricardo M. Biondi is working to control these enzymes, which are critical for the functioning of every cell. Thereby, he has a specific subgroup in his sights: the AGC protein kinases. Biondi’s point of attack is a structural region on the enzymes, which is known as the PIF-pocket. With the assistance of small chemical molecules that bind within this pocket, it is possible to either activate or inhibit these protein kinases.
In the first phase of GO-Bio funding from 2007, Biondi and his team not only identified and produced activators and inhibitors for the PIF-pockets, but also investigated a number of these in animal models. Alongside, the researchers used crystallographic methods to decipher the atomic details of the PIF-pockets of range of AGC protein kinases, as well as their modes of binding to active substances. In the second funding phase, Biondi is hoping to identify further suitable molecules using his own-developed screening platform as well as test the first cancer drug candidates in preclinical studies that will take place in the recently founded company PSites GmbH. At the end of the three-year funding period, it is intended to have a candidate ready for licensing to a pharmaceutical company for clinical trials and testing on humans.