PhD thesis enhanced with EU Lead Factory results and compounds

News
01 December 2016

The European Lead Factory is proud to announce the first doctoral promotion based on compounds screened with the EU Lead Factory project. On 1 December, Freek Janssen defends his thesis on drug discovery and target validation for the Leiden University.

Janssen investigated novel drug molecules under guidance of Dr Mario van der Stelt of the Molecular Physiology group at the Leiden Institute of Chemistry. One of the main targets, diacylglycerol lipase (DAGL), is a protein that makes endocannabinoids, the body’s own marijuana. Pharmacologically comparable to THC in marijuana, endocannabinoids have an effect on many physiological functions, such as emotional state or increased appetite (munchies). Janssen and his group used a target validation strategy to see if this protein could be a target for treatments of, for instance, obesity or neurodegenerative disorders. For his study he was rewarded by the European Federation of Medicinal Chemistry as the best oral presenter at the EFMC-YMCS’16.

Janssen started with an assay from the literature, that he adapted to comply with EU Lead Factory assay requirements. After it was accepted by the EU Lead Factory, the assay was further optimised and miniaturised. 'The expertise of the European Lead Factory is really impressive. I learned a lot about the approach of assay development.'

The European Lead Factory gave Janssen’s research a flying start. 'The access to the expertise and the very high quality drug-like compounds in the Joint European Compound Library is unique. We first screened a commercial library, but those hits could not be validated and I wasted a lot of time on deselection.'

Janssen’s thesis discloses for the first time ever chemical structures of EU Lead Factory qualified hit compounds. Several interesting chemotypes were discovered. One was actually already known by Janssen and his colleagues: 'Inspired by a patented structure, we published a compound series in 2013, but the EU Lead Factory analogues are actually much more promising. We have optimised them to attain a selective and drug-like compound.' Some of the developed compounds have been tested and showed promising results in an in vivo model.

Cooperating with the EU Lead Factory was not only beneficial for the research of Janssen. 'Currently there are three PhD students and several undergraduate students working on projects based on the QHL from EU Lead Factory.'  Together with the EU Lead Factory, Janssen was able to do what he likes best: to explore new territories, undiscovered grounds, and by that helping people that for instance inherited a disease: 'If I can contribute to that, with only a hit or a lead, that’s what I really like to do.' After a well-deserved holiday, Janssen looks forward to continue his career in biological chemistry. The research group of Mario van der Stelt will continue working with the targets; with the aim to eventually develop them into treatments for patients.  

We congratulate Freek Janssen with his PhD degree and wish him all the best in his future career! 

Read Freek Janssen's testimonial here