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

Figures & data

Table 1 Open-source model use across drug-repurposing activities

Drug-repurposing activity	Employment of open-source model	Examples of initiatives
Data mining for potential targets	Open databases providing target and drug profiles	DrugBank, Potential Drug Target Database, Therapeutic Target Database, SuperTarget, Open PHACTS
Data mining for potential candidates	Open databases providing chemical structural information	PubChem, ChMBL, ChemSpider, Orange Book – Discontinued Drug Products, FDA Rare Disease Repurposing Database
Search for potential compounds	Open compound repositories/chemical libraries	NCATS initiative; MRC/AstraZeneca partnership; Johns Hopkins Malaria Research Institute collaboration, CWHM, TRND, Wisdom Re:Search, OSDD
Compound screening	Shared screening tools/platforms	JHCCSI, NCATS-Lilly partnership, Sanford-Burnham Medical Research Institute screening program

Abbreviations: Open PHACTS, Open Pharmacological Space; FDA, US Food and Drug Administration; NCATS, National Center for Advancing Translational Sciences; MRC, Medical Research Council; CWHM, Center for World Health and Medicine; TRND, Therapeutics for Rare and Neglected Diseases; OSDD, Open Source Drug Discovery; JHCCSI, Johns Hopkins Clinical Compound Screening Initiative.

Table 2 Drug-repurposing initiatives sponsored by public sector, private sector, and nonprofit organizations

Public sector-driven initiative for drug repurposing	Private sector-driven initiative for drug repurposing	Nonprofit-driven initiative for drug repurposing
➢ NCATS initiative*	➢ New Indications Discovery Unit at the Novartis Institute for Biomedical Sciences	➢ Center for World Health and Medicine at Saint Louis University*
➢ MRC/AstraZeneca partnership*
➢ Clinical and Translational Science Award (CTSA) Pharmaceutical Assets Portal*	➢ Bayer Healthcare’s Common Mechanism Research	➢ WIPO Re:Search consortium*
		➢ The Johns Hopkins Clinical Compound Screening Initiative*
➢ NCATS-Lilly partnership	➢ Pfizer’s Indications Discovery Unit (IDU)
➢ CSIR-OSDD Initiative*	➢ Roche-Broad Institute partnership	➢ Cures Within Research*
		➢ The Learning Collaborative*
		➢ Sanford-Burnham Medical Research Institute*

Note:

* Programs that also focus on drug repurposing for rare and/or neglected diseases.

Abbreviations: NCATS, National Center for Advancing Translational Sciences; MRC, Medical Research Council; CSIR, Council of Scientific and Industrial Research; OSDD, Open Source Drug Discovery; WIPO, World Intellectual Property Organization.

Table 3 Models of collaboration, IP management, and human-capacity development employed by public and private sector-driven repurposing programs

Models of collaboration	Initiatives	Models of IP management	Initiatives	Models of human-capacity development	Initiatives
Data generation	NCATS initiative; IDMap; Open PHACTS; International; FDA’s Rare Disease Repurposing Database (RDRD) initiative; OSDD	Open source	MRC/AstraZeneca partnership; Open PHACTS; Johns Hopkins Clinical Compound Screening Initiative	Collaborative compound synthesis	CWHM pilot program; D3
Sharing and/or joint development of compounds	NCATS initiative; MRC/AstraZeneca partnership; Center for World Health and Medicine (CVVHM); Johns Hopkins Clinical Compound Screening; Sanford-Burnham Medical Research Institute; OSDD	IP separation based on usage	NCATS initiative	Collaborative opportunities at academic institutions	Via the Clinical and Translational Science Award (CTSA) Pharmaceutical Assets Portal
Joint model development	NCATS initiative; MRC/AstraZeneca partnership; Sanford-Burnham Medical Research Institute	Collaboration as an option to offer license	NCATS initiative; MRC-AstraZeneca Partnership; Lilly Phenotypic Drug Discovery (PD2); Roche-Broad Institute partnership; Learning Collaborative	Collaborative research at pharmaceutical organizations	WIPO Re:Search
Collaborative drug screening	Lilly Phenotypic Drug Discovery (PD2); Johns Hopkins Clinical Compound Screening Initiative; Sanford-Burnham Medical Research Institute; OSDD	Patent pool	WIPO Re:Search
Clinical development	MRC/AstraZeneca partnership; Cures Within Reach; OSDD	Royalty-free, open licensing	WIPO Re:Search

Abbreviations: Open PHACTS, Open Pharmacological Space; FDA, US Food and Drug Administration; NCATS, National Center for Advancing Translational Sciences; MRC; Medical Research Council; OSDD; Open Source Drug Discovery; CWHM, Center for World Health and Medicine; WIPO, World Intellectual Property Organization.

Table 4 Examples of repurposed drugs for NTDs

Drug	Original indication	Repurposing/repurposed for NTD
Astemizole	Antihistamine	Malaria
Avermectin	River blindness and elephantiasis	Tuberculosis
Miltefosine	Antineoplastic	Leishmaniasis
Tamoxifen	Anticancer	Leishmaniasis
Amphotericin B	Antifungal	Leishmaniasis
Eflornithine	Anticancer	African sleeping sickness
Phosphodiesterase-inhibitor analogues	Erectile dysfunction	African sleeping sickness; Chagas’s disease

Abbreviation: NTDs, neglected tropical diseases.

Figure 1 Neglected and Tropical Diseases Drug Repurposing Ecosystem.