CRIMALDDI: platform technologies and novel anti-malarial drug targets

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dc.contributor.authorVial, Henrien_ZA
dc.contributor.authorTaramelli, Donatellaen_ZA
dc.contributor.authorBoulton, Ianen_ZA
dc.contributor.authorWard, Steveen_ZA
dc.contributor.authorDoerig, Christianen_ZA
dc.contributor.authorChibale, Kellyen_ZA
dc.date.accessioned2015-11-27T09:35:22Z
dc.date.available2015-11-27T09:35:22Z
dc.date.issued2013en_ZA
dc.description.abstractThe Coordination, Rationalization, and Integration of antiMALarial drug Discovery & Development Initiatives (CRIMALDDI) Consortium, funded by the EU Framework Seven Programme, has attempted, through a series of interactive and facilitated workshops, to develop priorities for research to expedite the discovery of new anti-malarials. This paper outlines the recommendations for the development of enabling technologies and the identification of novel targets.Screening systems must be robust, validated, reproducible, and represent human malaria. They also need to be cost-effective. While such systems exist to screen for activity against blood stage Plasmodium falciparum, they are lacking for other Plasmodium spp. and other stages of the parasite's life cycle. Priority needs to be given to developing high-throughput screens that can identify activity against the liver and sexual stages. This in turn requires other enabling technologies to be developed to allow the study of these stages and to allow for the culture of liver cells and the parasite at all stages of its life cycle.As these enabling technologies become available, they will allow novel drug targets to be studied. Currently anti-malarials are mostly targeting the asexual blood stage of the parasite's life cycle. There are many other attractive targets that need to be investigated. The liver stages and the sexual stages will become more important as malaria control moves towards malaria elimination. Sexual development is a process offering multiple targets, even though the mechanisms of differentiation are still not fully understood. However, designing a drug whose effect is not curative but would be used in asymptomatic patients is difficult given current safety thresholds. Compounds active against the liver schizont would have a prophylactic effect and Plasmodium vivax elimination requires effectors against the dormant liver hypnozoites. It may be that drugs to be used in elimination campaigns will also need to have utility in the control phase. Compounds with activity against blood stages need to be screened for activity against other stages.Natural products should also be a valuable source of new compounds. They often occupy non-Lipinski chemical space and so may reveal valuable new chemotypes.en_ZA
dc.identifier.apacitationVial, H., Taramelli, D., Boulton, I., Ward, S., Doerig, C., & Chibale, K. (2013). CRIMALDDI: platform technologies and novel anti-malarial drug targets. <i>Malaria Journal</i>, http://hdl.handle.net/11427/15412en_ZA
dc.identifier.chicagocitationVial, Henri, Donatella Taramelli, Ian Boulton, Steve Ward, Christian Doerig, and Kelly Chibale "CRIMALDDI: platform technologies and novel anti-malarial drug targets." <i>Malaria Journal</i> (2013) http://hdl.handle.net/11427/15412en_ZA
dc.identifier.citationVial, H., Taramelli, D., Boulton, I. C., Ward, S. A., Doerig, C., & Chibale, K. (2012). CRIMALDDI: platform technologies and novel anti-malarial drug targets. Malaria journal, 12, 396-396.en_ZA
dc.identifier.ris TY - Journal Article AU - Vial, Henri AU - Taramelli, Donatella AU - Boulton, Ian AU - Ward, Steve AU - Doerig, Christian AU - Chibale, Kelly AB - The Coordination, Rationalization, and Integration of antiMALarial drug Discovery & Development Initiatives (CRIMALDDI) Consortium, funded by the EU Framework Seven Programme, has attempted, through a series of interactive and facilitated workshops, to develop priorities for research to expedite the discovery of new anti-malarials. This paper outlines the recommendations for the development of enabling technologies and the identification of novel targets.Screening systems must be robust, validated, reproducible, and represent human malaria. They also need to be cost-effective. While such systems exist to screen for activity against blood stage Plasmodium falciparum, they are lacking for other Plasmodium spp. and other stages of the parasite's life cycle. Priority needs to be given to developing high-throughput screens that can identify activity against the liver and sexual stages. This in turn requires other enabling technologies to be developed to allow the study of these stages and to allow for the culture of liver cells and the parasite at all stages of its life cycle.As these enabling technologies become available, they will allow novel drug targets to be studied. Currently anti-malarials are mostly targeting the asexual blood stage of the parasite's life cycle. There are many other attractive targets that need to be investigated. The liver stages and the sexual stages will become more important as malaria control moves towards malaria elimination. Sexual development is a process offering multiple targets, even though the mechanisms of differentiation are still not fully understood. However, designing a drug whose effect is not curative but would be used in asymptomatic patients is difficult given current safety thresholds. Compounds active against the liver schizont would have a prophylactic effect and Plasmodium vivax elimination requires effectors against the dormant liver hypnozoites. It may be that drugs to be used in elimination campaigns will also need to have utility in the control phase. Compounds with activity against blood stages need to be screened for activity against other stages.Natural products should also be a valuable source of new compounds. They often occupy non-Lipinski chemical space and so may reveal valuable new chemotypes. DA - 2013 DB - OpenUCT DO - 10.1186/1475-2875-12-396 DP - University of Cape Town J1 - Malaria Journal LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - CRIMALDDI: platform technologies and novel anti-malarial drug targets TI - CRIMALDDI: platform technologies and novel anti-malarial drug targets UR - http://hdl.handle.net/11427/15412 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15412
dc.identifier.urihttp://dx.doi.org/10.1186/1475-2875-12-396
dc.identifier.vancouvercitationVial H, Taramelli D, Boulton I, Ward S, Doerig C, Chibale K. CRIMALDDI: platform technologies and novel anti-malarial drug targets. Malaria Journal. 2013; http://hdl.handle.net/11427/15412.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDepartment of Chemistryen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2013 Vial et al.; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceMalaria Journalen_ZA
dc.source.urihttp://www.malariajournal.com/en_ZA
dc.subject.otherCRIMALDDIen_ZA
dc.subject.otherMalariaen_ZA
dc.subject.otherDrug discoveryen_ZA
dc.subject.otherResearch agendaen_ZA
dc.subject.otherNovel targetsen_ZA
dc.subject.otherEnabling technologiesen_ZA
dc.subject.otherPrioritizationen_ZA
dc.titleCRIMALDDI: platform technologies and novel anti-malarial drug targetsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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