Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-08

AUTHORS

Susan Wyllie, Michael Thomas, Stephen Patterson, Sabrinia Crouch, Manu De Rycker, Rhiannon Lowe, Stephanie Gresham, Michael D. Urbaniak, Thomas D. Otto, Laste Stojanovski, Frederick R. C. Simeons, Sujatha Manthri, Lorna M. MacLean, Fabio Zuccotto, Nadine Homeyer, Hannah Pflaumer, Markus Boesche, Lalitha Sastry, Paul Connolly, Sebastian Albrecht, Matt Berriman, Gerard Drewes, David W. Gray, Sonja Ghidelli-Disse, Susan Dixon, Jose M. Fiandor, Paul G. Wyatt, Michael A. J. Ferguson, Alan H. Fairlamb, Timothy J. Miles, Kevin D. Read, Ian H. Gilbert

ABSTRACT

Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis. More... »

PAGES

192-197

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41586-018-0356-z

DOI

http://dx.doi.org/10.1038/s41586-018-0356-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105808224

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30046105


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478 Drug Discovery Unit, Wellcome Centre for Anti-Infectives Research, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, UK
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