Validation of the protein kinase Pf CLK3 as a multistage cross-species malarial drug target-Reference-Cited by-同舟云学术

Validation of the protein kinase Pf CLK3 as a multistage cross-species malarial drug target

Published:2019-08-30 Issue:6456 Volume:365 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Alam Mahmood M.¹^ORCID,Sanchez-Azqueta Ana²^ORCID,Janha Omar²^ORCID,Flannery Erika L.³^ORCID,Mahindra Amit⁴^ORCID,Mapesa Kopano⁴,Char Aditya B.⁵^ORCID,Sriranganadane Dev⁶^ORCID,Brancucci Nicolas M. B.⁷^ORCID,Antonova-Koch Yevgeniya⁸^ORCID,Crouch Kathryn¹^ORCID,Simwela Nelson Victor¹^ORCID,Millar Scott B.¹,Akinwale Jude⁹^ORCID,Mitcheson Deborah¹⁰^ORCID,Solyakov Lev⁹,Dudek Kate⁹,Jones Carolyn⁹^ORCID,Zapatero Cleofé¹¹,Doerig Christian¹²^ORCID,Nwakanma Davis C.¹³^ORCID,Vázquez Maria Jesús¹¹,Colmenarejo Gonzalo¹⁴^ORCID,Lafuente-Monasterio Maria Jose¹¹^ORCID,Leon Maria Luisa¹¹^ORCID,Godoi Paulo H. C.⁶^ORCID,Elkins Jon M.¹⁵^ORCID,Waters Andrew P.¹^ORCID,Jamieson Andrew G.⁴,Álvaro Elena Fernández¹¹^ORCID,Ranford-Cartwright Lisa C.⁵^ORCID,Marti Matthias¹^ORCID,Winzeler Elizabeth A.⁸^ORCID,Gamo Francisco Javier¹¹^ORCID,Tobin Andrew B.²^ORCID

Affiliation:

1. Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow G12 8QQ, UK.

2. Centre for Translational Pharmacology, Institute of Molecular Cell and Systems Biology, University of Glasgow, Glasgow G12 8QQ, UK.

3. Novartis Institute for Biomedical Research, Emeryville, CA 94608, USA.

4. School of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK.

5. Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow G12 8QQ, UK.

6. Structural Genomics Consortium, Universidade Estadual de Campinas, Campinas, São Paulo 13083-886, Brazil.

7. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland.

8. Skaggs School of Pharmaceutical Sciences, UC Health Sciences Center for Immunology, Infection and Inflammation, University of California, San Diego, School of Medicine, La Jolla, CA 92093, USA.

9. Medical Research Council Toxicology Unit, University of Leicester, Leicester LE1 9HN, UK.

10. Department of Molecular Cell Biology, University of Leicester, Leicester LE1 9HN, UK.

11. Diseases of the Developing World, GlaxoSmithKline, 28760 Tres Cantos, Madrid, Spain.

12. Biomedical Science Cluster, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology, Melbourne, VIC 3000, Australia.

13. MRC Unit the Gambia, Fajara, Banjul, The Gambia.

14. Biostatistics and Bioinformatics Unit, IMDEA Food Institute, 28049 Madrid, Spain.

15. Structural Genomics Consortium, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Abstract

Targeting parasite's protein kinase Malaria elimination goals are constantly eroded by the challenge of emerging drug and insecticide resistance. Alam et al. have taken established drug targets—CLK protein kinases involved in regulation of RNA splicing—and investigated how inhibition of the parasite's enzymes blocks completion of its complex life cycle. They identified an inhibitor of the parasite's CLK protein kinase that was 100-fold less active against the most closely related human protein kinase and effective at clearing rodent malaria parasites. Not only does this compound halt the development of sexual stages but it also limits transmission to the mosquito vector of the parasite, a key requirement for malaria drugs. Science , this issue p. eaau1682

Funder

National Institutes of Health

Medical Research Council

University Of Glasgow

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference51 articles.

1. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates

2. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

3. Evidence of Plasmodium falciparum Malaria Multidrug Resistance to Artemisinin and Piperaquine in Western Cambodia: Dihydroartemisinin-Piperaquine Open-Label Multicenter Clinical Assessment

4. Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion

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