| Identification | Back Directory | [Name]
1-Pyrrolidinecarboxamide, N-[4-fluoro-3-[3-(4-morpholinyl)imidazo[1,2-a]pyrimidin-7-yl]phenyl]- | [CAS]
2080410-41-7 | [Synonyms]
GSK3494245
1-Pyrrolidinecarboxamide, N-[4-fluoro-3-[3-(4-morpholinyl)imidazo[1,2-a]pyrimidin-7-yl]phenyl]- | [Molecular Formula]
C21H23FN6O2 | [MOL File]
2080410-41-7.mol | [Molecular Weight]
410.44 |
| Hazard Information | Back Directory | [Uses]
GSK3494245 (DDD01305143) is a potent, orally active, and selective inhibitor of the chymotrypsin-like activity of the parasite proteasome binding in a site sandwiched between the β4 and β5 subunits (IC50=0.16 μM for WT L. donovani proteasomes). GSK3494245 moderately inhibits chymotrypsin-like activity of human proteasome (IC50: purified 26S=13 μM; enriched THP-1 extracts IC50=40μM). GSK3494245 exhibits attractive biological and biosafety properties[1][2]. | [in vivo]
GSK3494245 (25 mg/kg; orally twice a day for 10 consecutive days) elicits a >95% reduction of parasite load in Infected mice (L. donovani, LV9)[1]. | [References]
[1] Wyllie S, et al. Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition. Proc Natl Acad Sci U S A. 2019;116(19):9318-9323. DOI:10.1073/pnas.1820175116
[2] Thomas MG, et al. Identification of GSK3186899/DDD853651 as a Preclinical Development Candidate for the Treatment of Visceral Leishmaniasis. J Med Chem. 2019;62(3):1180-1202. DOI:10.1021/acs.jmedchem.8b01218 |
|
|