Almost twenty years after deciphering the human genome, our understanding of human disease is still far from complete. One of the most powerful and versatile tools to better understand biology and disease-relevant processes are well-characterized small chemical modulators of protein function. The newly formed public-private partnership “Enabling and Unlocking biology in the OPEN” (EUbOPEN) aims to develop high quality chemical tool compounds for 1,000 proteins (one third of the druggable proteins in the human body). It will enable unencumbered access to these research tools, thereby empowering academia and industry alike to explore disease biology and unlock the discovery of new drug targets and treatments.
The EUbOPEN consortium comprises 22 different partner organizations, including universities, research institutes, European Federation of Pharmaceutical Industries and Associations (EFPIA) members, and one small and medium-sized enterprise (SME). Goethe University Frankfurt and Boehringer Ingelheim are jointly leading the EUbOPEN consortium.
The University of Dundee is one of those partner organisations through the team of Professor Alessio Ciulli in the School. They bring to the consortium expertise in targeting E3 ubiquitin ligases with small molecule inhibitors and degraders, for example PROTACs. PROTACs are revolutionalizing drug discovery and there is plenty of scope to expand the E3 ligases beyond the handful that are utilised currently. The Ciulli lab have a long-standing track record with developing potent and selective ligands for one of the most popular E3 ligase, VHL, amongst others. Their expertise with applying structure-guided fragment-based design approaches to the development of chemical probes will augment the collaborative and interdisciplinary efforts within the consortium.
Alessio Ciulli, Professor of Chemical and Structural Biology, said, “We at Dundee feel excited and privileged to contribute to the newly formed EUbOPEN consortium. The focus on E3 ligases amongst other target classes fits right at the heart of the remit and focus of Dundee’s new Protein Degradation Centre. This consortium is a first step toward a long-term goal of achieving small molecule probes for most human proteins as a unique resource for innovation. We share the consortium ethos for open science. No single lab can be successful on their own at tackling such a major challenge. To accelerate the discovery process and maximise impact we must bring together key expertise and share findings in an open and collaborative manner.”
The generation and dissemination of high-quality and well-characterized research tools for a substantial fraction of the druggable human genome are the major goals of this large consortium. EUbOPEN was launched on 1 May 2020, with a total budget of 65.8 million euros covered by a grant from the Innovative Medicines Initiative (IMI) and cash/in-kind contributions from EFPIA companies, IMI Associated Partners and from partners outside of Europe.
“EUbOPEN will provide the wider academic community with unencumbered access to the highest quality pharmacological tool compounds for a large number of novel targets, and seed a massive community target prioritization and deconvolution effort. The expected impact should be transformative”, says Project Leader Adrian J. Carter, Boehringer Ingelheim.
EUbOPEN will develop these compounds using new technologies and test them in well-characterized, disease-relevant human tissue assays in the areas of immunology, oncology and neuroscience. The project outputs, including chemogenomic library sets, chemical probes, assay protocols and associated research data will be made openly available to the research community without restriction.
About the EUbOPEN consortium
The EUbOPEN consortium comprises 22 different partner organizations, including universities, research institutes, European Federation of Pharmaceutical Industries and Associations (EFPIA) members, and one small and medium-sized enterprise (SME). Goethe University Frankfurt and Boehringer Ingelheim are jointly leading the EUbOPEN consortium. Other partner organizations are Bayer AG, Diamond Light Source, EMBL-EBI, ETH Zürich, Fraunhofer IME, Georg Speyer Haus, Karolinska Institutet, Leiden University Medical Center, McGill University, Ontario Institute for Cancer Research, Pfizer, Royal Institute of Technology, Servier, the Structural Genomics Consortium, Takeda, University of Dundee, University of North Carolina, University of Oxford, and University of Toronto.
Acknowledgement
This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 875510. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme, five EFPIA members, KTH, Diamond Light Source, OICR and McGill University.