CRIMALDDI: platform technologies and novel anti-malarial drug targets

Malaria Journal

Commentary

Henri Vial¹  Kelly Chibale²  Christian Doerig³  Donatella Taramelli⁴  Steve A Ward⁵  Ian C Boulton⁶ 

[1] Centre National de la Recherche Scientifique, UMR 5235, Université Montpellier 2, Place Eugene Bataillon, 34095, Cedex 5, Montpellier, France;Department of Chemistry, University of Cape Town, 7701, Rondebosch, Cape Town, South Africa;Department of Microbiology, School of Biomedical Sciences, Monash University, Wellington Road, 3800, Clayton, VIC, Australia;Dipartmento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Via Pascal 36, 20133, Milano, Italy;Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK;TropMed Pharma Consulting Ltd, 10 Brampton Chase, RG9 3BX, Lower Shiplake, Oxfordshire, UK;

关键词: CRIMALDDI;    Malaria;    Drug discovery;    Research agenda;    Novel targets;    Enabling technologies;    Prioritization;   

DOI  :  10.1186/1475-2875-12-396

 received in 2013-07-17, accepted in 2013-10-22,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Vial et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.