Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis.
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ABSTRACT:
SUBMITTER: Wyllie S
PROVIDER: S-EPMC6402543 | biostudies-literature | 2018 Aug
REPOSITORIES: biostudies-literature
Publications
Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis.
Wyllie Susan S Thomas Michael M Patterson Stephen S Crouch Sabrinia S De Rycker Manu M Lowe Rhiannon R Gresham Stephanie S Urbaniak Michael D MD Otto Thomas D TD Stojanovski Laste L Simeons Frederick R C FRC Manthri Sujatha S MacLean Lorna M LM Zuccotto Fabio F Homeyer Nadine N Pflaumer Hannah H Boesche Markus M Sastry Lalitha L Connolly Paul P Albrecht Sebastian S Berriman Matt M Drewes Gerard G Gray David W DW Ghidelli-Disse Sonja S Dixon Susan S Fiandor Jose M JM Wyatt Paul G PG Ferguson Michael A J MAJ Fairlamb Alan H AH Miles Timothy J TJ Read Kevin D KD Gilbert Ian H IH
Nature 20180725 7717
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 prope ...[more]
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