LXE408 is an orally active, non-competitive and kinetoplastid-selective proteasome inhibitor. LXE408 has an IC 50 of 0.04 μM for L. donovani proteasome and an EC 50 of 0.04 μM for L. donovani. LXE408 has a low propensity to cross the blood brain barrier. LXE408 has the potential for visceral leishmaniasis (VL) research. In Vitro LXE408 (compound 1) can occupy the pocket as a ternary complex with the proteasome. LXE408 shows no inhibition of the hERG channel (IC 50 >30 μM) in a manual patch clamp assay. LXE408 has a low propensity to cross the blood brain barrier (brain/plasma AUC ratio=0.03 in mice). MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo LXE408 (compound 1; 0.3-10 mg/kg; PO; twice daily for 8 days) potently reduces the parasite burden in the liver in a dose-dependent manner . LXE408 (1, 3, 10, 20 mg/kg; p.o.; b.i.d.; for 10 days) effects robust healing of parasite-induced skin lesions at the base of the tail in BALB/c mice infected with L. major . LXE408 (5 mg/kg IV and 20 mg/kg PO) has a T 1/2 of 3.3 hours for mouse. LXE408 (3 mg/kg IV and 10 mg/kg PO) has a T 1/2 of 3.8 hours, a CL of 2.1 mL/min•kg, and a V ss of 0.53 L/kg for male Sprague-Dawley rat . LXE408 (0.3 mg/kg IV and 1.0 mg/kg PO) has a T 1/2 of 3.8 hours for male beagle dog. LXE408 (0.3 mg/kg IV and 10 mg/kg PO) has a T 1/2 of 9.7 hours for male cynomolgus monkey . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female BALB/c mice (6-8 weeks old) infected with L. donovani Dosage: 0.3, 1, 3, 10 mg/kg Administration: PO; twice daily for 8 days Result: Led to a 95% and >99.84% reduction of parasite burden in the liver at 1 mg/kg and 10 mg/kg. Animal Model: Balb/C mice Dosage: 5 mg/kg IV and 20 mg/kg PO (Pharmacokinetic Analysis) Administration: IV or PO Result: Had a T 1/2 of 3.3 hours, a CL of 2.3 mL/min•kg, and a V ss of 0.63 L/kg for mouse. Form:Solid