The research work of the Moglynet Consortium was structured into two priority activities i) the scientific and ii) the training programme.
i) The scientific project was structured into three WPs, corresponding to the different objectives.
Two different strategies were pursued to achieve glycolysis inhibition that represents an attractive therapeutic approach to reduce pathological neovascularization and to delay the progression of plaque or induce regression, controlling excessive inflammation and improper immune response. Libraries of small molecules targeted to the kinase pocket and peptides targeting an allosteric site of PFKFB3 were designed and synthesized. The potential role of these modulators - and other glycolytic pathway flux key players - in endothelial dysfunctionality associated to comorbidities in patients with atherosclerosis was investigated.
In summary the main goals achieved in terms of targeting angiogenesis are
a) the selection of very active PFKFB3-Kinase modulators significantly suppressing the key steps of inflammatory angiogenesis and markedly impaired capillary-like tube formation. One of them was radio-synthesised and tested in vitro and in vivo, showing capacity and potential to image the atherosclerotic plaque in mice using Positron Emission Tomography;
b) the demonstration that 3PO inhibits glycolysis and angiogenesis in a PFKFB3-independent manner;
c) an innovative and indirect strategy for the modulation of PFKFB3 activity was achieved through allosteric bisphosphatase modulation. This new strategy might be of interest for achieving a finer regulation of glycolysis without the risk of an off-target interaction with other kinases. The identified compounds could be valuable probes to study PFKFB3 under a so far unexplored condition.
ii) Training activity. One of the main aims of the Moglynet programme has been to create a common knowledge and language for the next generation of researchers working in the highly multidisciplinary field of drugs design and development. Several courses and workshops were organized with different scientific topics related to the project, and two summer schools on i) “PET Imaging and Radiopharmaceutical Development” and ii) “Pharma skills” open to external scientists. Advanced courses on specific topics were delivered at the six Doctoral Courses/Schools of the five beneficiary institutions.
Dissemination Activity. The Consortium paved the way to establish fruitful communication and dissemination strategy about the Moglynet activities.
- The Moglynet website (
http://www.moglynet.com/website/(si apre in una nuova finestra)) a Moglynet Brochure were created
- a video on the Moglynet Consortium was produced (
https://www.youtube.com/watch?v=f4UTwbVshnk)(si apre in una nuova finestra);
- Articles on non-specialized press/Blogs were delivered (PLATINUM - BUSINESS LEADERS, IMPACT, Universiteit Antwerpen Magazine etc)
- Events “Tu lo conosci il farmaco”
http://portalevideo.unimi.it/media?mid=664(si apre in una nuova finestra) for students of secondary schools; FOS and AIO at Leiden and others were delivered.
- 70 posters/oral communications were delivered by ESRs.
- 27 open-access scientific papers on peer reviewed journals were published.
- Events “Tu lo conosci il farmaco”
http://portalevideo.unimi.it/media?mid=664(si apre in una nuova finestra) for students of secondary schools; FOS and AIO at Leiden and others were delivered.
- 70 posters/oral communications were delivered by ESRs.
- 27 open-access scientific papers on peer reviewed journals were published.
