Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases

Abstract

Repurposing has the objective of targeting existing drugs and failed, abandoned, or yet-to-be-pursued clinical candidates to new disease areas. The open-source model permits for the sharing of data, resources, compounds, clinical molecules, small libraries, and screening platforms to cost-effectively advance old drugs and/or candidates into clinical re-development. Clearly, at the core of drug-repurposing activities is collaboration, in many cases progressing beyond the open sharing of resources, technology, and intellectual property, to the sharing of facilities and joint program development to foster drug-repurposing human-capacity development. A variety of initiatives under way for drug repurposing, including those targeting rare and neglected diseases, are discussed in this review and provide insight into the stakeholders engaged in drug-repurposing discovery, the models of collaboration used, the intellectual property-management policies crafted, and human capacity developed. In the case of neglected tropical diseases, it is suggested that the development of human capital be a central aspect of drug-repurposing programs. Open-source models can support human-capital development through collaborative data generation, open compound access, open and collaborative screening, preclinical and possibly clinical studies. Given the urgency of drug development for neglected tropical diseases, the review suggests elements from current repurposing programs be extended to the neglected tropical diseases arena.

The curious stories of drugs with two lives: a new paradigm in drug development

“…Other approaches are set out to use complex mathematical computational models, where drug attributes and possible receptor affinities can be matched with target proteins or receptors known to exist in a particular disease state. 18,19 Such models have made detailed studies of a drugs molecular structure and side chains and then matched them with drugs with similar structural properties that are known to be effective in the target illness. 19 Lastly, there are already in existence vast data banks such as OpenPhacts, DrugBank and the delightfully named 'Promiscuous' that provide a wealth of pharmacological and physicochemical data, as well as information on drugs' protein and active-site structures and associations with related disease states, 20 that lie ready to be mined.…”

“…18,19 Such models have made detailed studies of a drugs molecular structure and side chains and then matched them with drugs with similar structural properties that are known to be effective in the target illness. 19 Lastly, there are already in existence vast data banks such as OpenPhacts, DrugBank and the delightfully named 'Promiscuous' that provide a wealth of pharmacological and physicochemical data, as well as information on drugs' protein and active-site structures and associations with related disease states, 20 that lie ready to be mined. These existence of data banks, together with the fact that a new journal entirely devoted to the subject of drug repositioning is to be launched shortly, 21 suggest that drug repositioning may indeed herald a new dawn in the complex world of drug discovery and development.…”

The successes and challenges of open-source biopharmaceutical innovation

“…Open-source databases such as DrugBank, the Potential Drug Target Database, Therapeutic Target Database and SuperTarget provide target and drug profiles [2][3][4][5]. These databases feature drug targets, including protein and active site structures, association with related diseases, biological functions and associated signaling pathways [3].…”

“…ChemProt, a disease chemical biology database, is based on a collection of multiple chemical-protein annotation resources, as well as disease-associated protein--protein interactions [6]. Moving further downstream, compound-specific databases comprise PubChem, ChEMBL and ChemSpider [2]. Hinting at the need for data integration and standardization is Open Babel.…”

“…Arising then out of these collaborations should be human capacity engagement through educational and other training opportunities. I have discussed the SGC visitor training program as one example and we see the recently established WIPO Re:Search initiative offering educational and training opportunities for researchers within the private sector context [2].…”