The European lead factory—an experiment in collaborative drug discovery

Authors

    Hugh Laverty, Kristina Maria Orrling, Fabrizio Giordanetto, Magali Poinot, Eckhard Ottow, Ton Wilhelmus Rijnders, Dimitrios Tzalis, Stefan Jaroch

DOI:

https://doi.org/10.18063/jmds.v1i1.120

Keywords:

drug discovery, public–private partnership, ultra-high throughput screening, biological targets, chemistry scaffolds, honest data broker, qualified hit list, European Screening Centre, biomedical innovation, Joint European Compound Collection

Abstract

The European Lead Factory (ELF) is a unique collaborative public–private partnership aiming to deliver innovative drug discovery starting points and improving the value generated by ultra-High Throughput Screening (uHTS) approaches. Composed of a unique compound collection derived from private pharmaceutical company collections and complemented with new chemistries from a unique public collection, it offers a unique uHTS platform accessible to both private companies and publicly funded researchers. One of the key challenges in setting up ELF has been to balance access to screening results with protecting the value of compounds in the collection. Through an ‘honest data broker’ data management platform and a royalty reward scheme based on achieved milestones, ELF has been able to overcome these challenges. Set up in 2013, it has already accepted 42 targets for screening, submitted by publicly funded researchers, and generated 12 Qualified Hit Lists. In addition, 55,000 new library compounds have been generated by the public partners and added to the 320,000 compounds made available by the companies. Although it faced many challenges in becoming operational, this unique experiment in collaboration is already generating exciting results that will hopefully, eventually lead to better medicines and tools to advance our biological knowledge, and should act as a template for future approaches in the area.

References

Schmid E F and Smith D A, 2007, Pharmaceutical R&D in the spotlight: Why is there still unmet medical need? Drug Discovery Today, vol.12(23–24): 998–1006.

Hay M, Thomas D W, Craighead J L, et al. 2014, Clinical development success rates for investigational drugs. Nature Biotechnology, vol.32: 40–51. http://dx.doi.org/10.1038/nbt.2786.

Khanna I, 2012, Drug discovery in pharmaceutical industry: Productivity challenges and trends. Drug Discovery Today, vol.17(19–20): 1088–1102. http://dx.doi.org/10.1016/j.drudis.2012.05.007.

Macarron R, Banks M N, Bojanic D, et al. 2011, Impact of high-throughput screening in biomedical research. Nature Reviews Drug Discovery, vol.10: 188–195. http://dx.doi.org/10.1038/nrd3368.

, Screening we can believe in. Nature Chemical Biology, vol.5: 127

Kogej T, Blomberg N, Greasley P J, et al. 2013, Big pharma screening collections: More of the same or unique libraries? The AstraZeneca-Bayer Pharma AG case. Drug Discovery Today, vol.18: 1014–1024. http://dx.doi.org/10.1016/j.drudis.2012.10.011.

Schamberger J, Grimm M, Steinmeyer A, et al. 2011, Rendezvous in chemical space? Comparing the small molecule compound libraries of Bayer and Schering. Drug Discovery Today, vol.16: 636–641. http://dx.doi.org/10.1016/j.drudis.2011.04.005.

Goldman M, 2012, The innovative medicines initiative: AEuropean response to the innovation challenge. Clinical Pharmacology and Therapeutics, vol.91(3): 418–425. http://dx.doi.org/10.1038/clpt.2011.321.

Wang L, Plump A and Ringel M, 2015, Racing to define pharmaceutical R&D external innovation models. Drug Discovery Today, vol.20(3): 361–370. http://dx.doi.org/10.1016/j.drudis.2014.10.008.

Bentzien J, Bharadwaj R and Thompson D C, 2015, Crowdsourcing in pharma: A strategic framework. Drug Discovery Today, vol.S1359–6446(15): 00033–1. http://dx.doi.org/10.1016/j.drudis.2015.01.011.

Schuhmacher A, Germann P G, Trill H, et al. 2013, Models for open innovation in the pharmaceutical industry. Drug Discovery Today, vol.18(23–24): 1133–1137. http://dx.doi.org/10.1016/j.drudis.2013.07.013.

Jones A and Clifford L, 2005, From the analyst’s couch: Drug discovery alliances. Nature Reviews Drug Discovery, vol.4: 807–808. http://dx.doi.org/10.1038/nrd1856.

Dahlin J L, Inglese J and Walters M A, 2015, Mitigating risk in academic preclinical drug discovery. Nature Reviews Drug Discovery, vol.14: 279–294. http://dx.doi.org/10.1038/nrd4578.

Munos B, 2010, Can open-source drug R&D repower pharmaceutical innovation? Clinical Pharmacology and Therapeutics, vol.87(5): 534–536. http://dx.doi.org/10.1038/clpt.2010.26.

Besnard J, Jones P S, Hopkins A L, et al. 2015, The Joint European Compound Library: Boosting precompetitive research. Drug Discovery Today, vol.20: 181–186. http://dx.doi.org/10.1016/j.drudis.2014.08.014.

Frye S, Crosby M, Edwards T, et al. 2011, US academic drug discovery. Nature Review Drug Discovery, vol.10: 409–410. http://dx.doi.org/10.1038/nrd3462.

Tralau-Stewart C, Low C M R, and Marlin N, 2014, UK academic drug discovery. Nature Review Drug Discovery, vol.13(1): 15–16. http://dx.doi.org/10.1038/nrd4200.

Bolton E, Wang Y, Thiessen P A, et al. 2008, PubChem: Integrated platform of small molecules and biological activities, in Wheeler R A and Spellmeyer D C, eds. Annual Reports in Computational Chemistry, Volume 4. Elsevier, Oxford, 217–241. http://dx.doi.org/10.1016/S1574-1400(08)00012-1.

Bento A P, Gaulton A, Hersey A, et al. 2014, The ChEMBL bioactivity database: An update. Nucleic Acids Research, 42(Database issue): D1083–D1090 http://dx.doi.org/10.1093/nar/gkt1031.

Chemistry Workflow Solution/Elsevier n.d., viewed May 1, 2015,

SciFinder - The choice for chemistry research n.d., viewed May 1, 2015,

Teague S J, Davis A M, Leeson P D, et al. 1999, The design of leadlike combinatorial libraries. Angewandte Chemie International ed. in English, vol.38(24): 3743– 3748.

Colomer I, Adeniji O, Burslem G M, et al. 2015, Aminomethylhydroxylation of alkenes: Exploitation in the synthesis of scaffolds for small molecule libraries. Bioorganic & Medicinal Chemistry, vol.23(11): 2736–2740. http://dx.doi.org/10.1016/j.bmc.2015.01.058.

Petersen M X, Mortensen M A, Cohrt A E, et al. 2015, Synthesis of 1,4,5 trisubstituted γ-lactams via a 3-component cascade reaction. Bioorganic & Medicinal Chemistry, vol.23(11): 2695–2698. http://dx.doi.org/10.1016/j.bmc.2015.01.041.

Patil P, Khoury K, Herdtweck E, et al. 2014, MCR synthesis of a tetracyclic tetrazole scaffold. Bioorganic & Medicinal Chemistry, vol.23(11): 2699–2715. http://dx.doi.org/10.1016/j.bmc.2014.12.021.

Craven P, Aimon A, Dow M, et al. 2014, Design, synthesis and decoration of molecular scaffolds for exploitation in the production of alkaloid-like libraries. Bioorganic & Medicinal Chemistry, vol.23(11): 2629– 2635. http://dx.doi.org/10.1016/j.bmc.2014.12.048.

Murali A, Medda F, Winkler M, et al. 2015, Branching cascades provide access to two amino-oxazoline compound libraries. Bioorganic & Medicinal Chemistry, vol.23(11): 2656–2665. http://dx.doi.org/10.1016/j.bmc.2015.01.009.

Sankar M G, Mantilli L, Bull J, et al. 2015, Stereoselective synthesis of a natural product inspired tetrahydroindolo[2,3-a]-quinolizine compound library. Bioorganic & Medicinal Chemistry, vol.23(11): 2614–2620. http://dx.doi.org/10.1016/j.bmc.2015.01.019.

Ortega R, Sanchez-Quesada J, Lorenz C, et al. 2015, Design and synthesis of 1,1-disubstituted-1-silacyclo-alkane-based compound libraries. Bioorganic & Medicinal Chemistry, vol.23(11): 2716–2720. http://dx.doi.org/10.1016/j.bmc.2015.01.046.

Petersen R, Cohrt A E, Petersen M X, et al. 2015, Synthesis of hexahydropyrrolo[2,1-a]isoquinoline compound libraries through a Pictet-Spengler cyclization/metal-catalyzed cross coupling/amidation sequence. Bioorganic & Medicinal Chemistry, vol.23(11): 2646–2649. http://dx.doi.org/10.1016/j.bmc.2015.01.039.

Padwal J D, Filippov D V, Narhe B D, et al. 2015, Cyclopentitol as a scaffold for a natural product-like compound library for drug discovery. Bioorganic & Medicinal Chemistry, vol.23(11): 2650–2655. http://dx.doi.org/10.1016/j.bmc.2015.01.040.

Van der Pijl F, van Delft F L and Rutjes F P, 2015, Synthesis and functionalization of bicyclic N,O-acetal scaffolds from furfural. Bioorganic & Medicinal Chemistry, vol.23(11): 2721–2729. http://dx.doi.org/10.1016/j.bmc.2014.12.045.

Storr T E, Cully S J, Rawling M J, et al. 2014, Combining two-directional synthesis and tandem reactions. Part 21: Exploitation of a dimeric macrocycle for chain terminus differentiation and synthesis of an sp3-rich library. Bioorganic & Medicinal Chemistry, vol.23(11): 2621–2628 http://dx.doi.org/10.1016/j.bmc.2014.12.050.

Nortcliffe A. and Moody C J, 2015, Seven-membered ring scaffolds for drug discovery: Access to functionalised azepanes and oxepanes through diazocarbonyl chemistry. Bioorganic & Medicinal Chemistry, vol.23(11): 2730–2735. http://dx.doi.org/10.1016/j.bmc.2015.01.010.

NTRC bv receives Qualified Hit series for TDO from the European Lead Factory n.d., viewed April 21, 2014,

Austin C P, Brady L, Insel T R, et al. 2004, NIH Molecular Libraries Initiative. Science, vol.306:1138–1139.

ELF Press Release n.d., viewed April 22, 2014,

Downloads

Published

2016-07-21