Abstract
ABSTRACTOpen-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages in vitro. Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this in vitro biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research.
Highlights
The face of drug discovery is continually changing and never more so than in the last 5 to 10 years where early-stage drug discovery has transitioned to extend beyond the traditional domain of large pharmaceutical companies
The open drug discovery approach can be described by several models as recently defined by Wells et al (Medicines for Malaria Venture [Medicines Malaria Venture (MMV)]) in which malaria drug discovery is discussed in the open arena [11]
The details for all compounds, excluding the reference compound set from the Pathogen Box (PBox) supporting information Excel file, are aligned and merged with the biological activity obtained from the evaluation undertaken within Discovery Biology
Summary
The face of drug discovery is continually changing and never more so than in the last 5 to 10 years where early-stage drug discovery has transitioned to extend beyond the traditional domain of large pharmaceutical companies. The open drug discovery approach can be described by several models as recently defined by Wells et al (Medicines for Malaria Venture [MMV]) in which malaria drug discovery is discussed in the open arena [11] The success of this approach is not limited to malaria [12,13,14,15,16] and includes a number of diseases, such as tuberculosis [17, 18], schistosomiasis [19,20,21], diseases caused by kinetoplastids [22], toxoplasmosis [23], and cryptosporidiosis [24]; in addition, treatments for diseases caused by other viral and bacterial pathogens have benefited. The demonstration of inhibitory activity against Candida albicans biofilm formation by MMV688768 (an original indication for schistosomiasis) [28]
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