| Identification | Back Directory | [Name]
GSK3186899 | [CAS]
1972617-87-0 | [Synonyms]
GSK3186899
DDD-853651
1-Propanesulfonamide, 3,3,3-trifluoro-N-[trans-4-[[3-[(2S)-2-methyl-4-morpholinyl]-1H-pyrazolo[3,4-d]pyrimidin-6-yl]amino]cyclohexyl]- | [Molecular Formula]
C19H28F3N7O3S | [MDL Number]
MFCD31692411 | [MOL File]
1972617-87-0.mol | [Molecular Weight]
491.53 |
| Hazard Information | Back Directory | [Description]
GSK3186899, also known as DDD-853651, is a CDC2-related kinase 12 inhibitor (CRK12), with an EC50 of 1.4 μM. GSK3186899 is an candidate for the Treatment of Visceral Leishmaniasis. | [Uses]
GSK3186899 (DDD-853651) is an inhibitor of cdc-2-related kinase 12 (CRK12), with an EC50 of 1.4 μM for L. donovani in an intra-macrophage assay. | [in vivo]
In the mouse model of infection, GSK3186899 demonstrates comparable activity to the front-line drug miltefosine, reducing parasite levels by 99% when dosed orally twice a day for 10 days at 25 mg/kg. The efficacy of treatment is dependent on dose, frequency, and duration (10 days better than 5). The non-clinical safety data for GSK3186899 suggests a suitable therapeutic window for progression into regulatory preclinical studies. Non-GLP preclinical assessment of cardiovascular effects and genotoxicity does not reveal any issues that would prevent further development. In addition, there are no notable adverse effects in a rat seven-day repeat-dose oral toxicity study with respect to clinical chemistry and histopathology at all doses tested. Both the in vivo efficacy and safety profile of GSK3186899 support progression to definitive safety studies[1]. | [IC 50]
Leishmania | [storage]
Store at -20°C | [References]
[1] Wyllie S, et al. Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis. Nature. 2018 Aug;560(7717):192-197. DOI:10.1038/s41586-018-0356-z |
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