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Open Lab as a source of hits and leads against tuberculosis, malaria and kinetoplastid diseases

Nature Reviews Drug Discovery volume 15, page 292 (2016)Cite this article

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In their recent paper (Hit and lead criteria for drug discovery for infectious diseases of the developing world. Nat. Rev. Drug Discov. 14, 751–758 (2015))1, Katsuno et al. present a set of useful guiding criteria on what constitutes a hit or a lead to initiate a drug discovery programme against tuberculosis (TB), malaria or kinetoplastid infections. But what will be the origin of future small-molecule starting points? What mechanisms are currently in place to ensure that the early-stage pipeline for diseases of the developing world remains healthy? Taking stock from epidemiological realities in areas such as microbial infections, a sustainable research and development (R&D) effort to address the continuous threat of drug resistance will be required. This effort will need to go beyond the earlier phase of 'standardized' phenotypic screening, in which hit molecules were identified and progressed by virtue of their anti-proliferative activity against parasites and bacteria. This potential gap is further compounded by the slow but steady shift of focus and funding from preclinical to clinical research as the current pipeline matures and the naturally high attrition rates affecting drug discovery continue unabated. For this phase, new community-wide R&D models based on continuous and open innovation will be required to re-invigorate hit- and lead-identification activities.

The Tres Cantos Medicines Development Campus (TCMDC) was established with the aim of contributing to the GlaxoSmithKline (GSK) vision of open-source drug discovery for diseases of the developing world. The first step in GSK's open-innovation strategy involved the public release of proprietary data generated during various drug-screening campaigns, exemplified in the Tres Cantos antimalarial, antitubercular and antikinetoplastid compound collections and data sets2,3,4,5. The objective of releasing this information through a number of freely accessible databases was to provide small molecules as starting points for synthetic drug lead generation by the wider scientific community. As a result, GSK compound sets have been shared with over 300 academic laboratories worldwide. In two instances, derivatives of compounds present in the publicly available data sets progressed to become clinical candidates for the treatment of malaria6,7. Albeit a crucial first step to initiate collaborative research, it was envisaged that the release of proprietary screening data would not be sufficient to facilitate the creation of a virtual community of scientists working on a sustainable pipeline for diseases of the developing world, and questions remained about how best to articulate, coordinate and financially sustain such a community. These concerns underpinned the creation of the Tres Cantos Open Lab Foundation (TCOLF).

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Figure 1: Overview of ongoing efforts to target malaria, kinetoplastid infection and tuberculosis.

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Authors and Affiliations

  1. Department of Diseases of the Developing World, GlaxoSmithKline, Parque Tecnológico de Madrid, Calle de Severo Ochoa, 2, Tres Cantos, Madrid, 28760, Spain

    Lluís Ballell, Mike Strange & Nicholas Cammack

  2. Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK

    Alan H. Fairlamb

  3. Department of Medicine, University of Cambridge, Cambridge, CB2 0SP, UK

    Leszek Borysiewicz

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  1. Lluís Ballell
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  2. Mike Strange
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  4. Alan H. Fairlamb
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Correspondence to Lluís Ballell.

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Competing interests

L. Ba., M.S. and N.C. are currently employees of GlaxoSmithKline and share stock in the company. L. Bo. and A.F. are currently Board members and Trustees of the Tres Cantos Open Lab Foundation.

Supplementary information

Supplementary information S1 (figure)

Schematic representation of the impact of GlaxoSmithKline and Tres Cantos Open Lab Foundation (TCOLF) activities on the current global preclinical and clinical portfolios for tuberculosis (TB), malaria and kinetoplastid infection. (PDF 195 kb)

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Ballell, L., Strange, M., Cammack, N. et al. Open Lab as a source of hits and leads against tuberculosis, malaria and kinetoplastid diseases. Nat Rev Drug Discov 15, 292 (2016). https://doi.org/10.1038/nrd.2016.51

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