2080410-41-7

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].

[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