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Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis
- Source :
- Nature
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
Proteomics
Proteome
030106 microbiology
Leishmania donovani
Druggability
Disease
Pharmacology
Pyrazolopyrimidine
Article
Substrate Specificity
03 medical and health sciences
chemistry.chemical_compound
Mice
Cyclin-dependent kinase
Medicine
Animals
Humans
Molecular Targeted Therapy
Multidisciplinary
biology
business.industry
Kinase
Reproducibility of Results
Leishmaniasis
biology.organism_classification
medicine.disease
Cyclin-Dependent Kinase 9
Cyclin-Dependent Kinases
3. Good health
Molecular Docking Simulation
Disease Models, Animal
030104 developmental biology
Visceral leishmaniasis
Pyrimidines
chemistry
biology.protein
Leishmaniasis, Visceral
Pyrazoles
business
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 560
- Issue :
- 7717
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....7b6f9bff9da702dd0f4d789ce1ce05a4