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GSK3494245 (DDD01305143) is a potent, selective, orally active inhibitor of chymotrypsin-like activity that binds to the proteasome of WTL.donovani at an IC50 of 0.16 μM, sandwiched between the β4 and β5 subunits. GSK3494245 exhibits good biosafety properties. GSK3494245 is a suitable inhibitor of the chymotrypsin-like activity of the human proteasome (IC50: 26S=13 μM; enriched THP-1 extract IC50=40 μM).