AI Article Synopsis
- Visceral leishmaniasis is a significant health issue worldwide, causing high rates of illness and death, highlighting the urgent need for new treatments.
- Researchers developed a series of potential anti-leishmanial drugs based on a chemical structure called pyrazolopyrimidine, with the most promising compound being DDD853651/GSK3186899.
- This leading compound has shown effectiveness in treating the disease in mouse models and works mainly by inhibiting a specific parasite enzyme (CRK12), making it a viable candidate for further drug development.
Article 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402543 | PMC |
| http://dx.doi.org/10.1038/s41586-018-0356-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!