| Identification | Back Directory | [Name]
5-Oxazolecarboxamide, N-[4-fluoro-3-[6-(3-methyl-2-pyridinyl)[1,2,4]triazolo[1,5-a]pyrimidin-2-yl]phenyl]-2,4-dimethyl- | [CAS]
1799330-15-6 | [Synonyms]
5-Oxazolecarboxamide, N-[4-fluoro-3-[6-(3-methyl-2-pyridinyl)[1,2,4]triazolo[1,5-a]pyrimidin-2-yl]phenyl]-2,4-dimethyl- | [Molecular Formula]
C23H18FN7O2 | [MOL File]
1799330-15-6.mol | [Molecular Weight]
443.43 |
| Chemical Properties | Back Directory | [density ]
1.46±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [form ]
Solid | [pka]
10.36±0.70(Predicted) | [color ]
Off-white to light yellow |
| Hazard Information | Back Directory | [Uses]
LXE408 is an orally active, non-competitive and kinetoplastid-selective proteasome inhibitor. LXE408 has an IC50 of 0.04 μM for L. donovani proteasome and an EC50 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[1]. | [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[1].
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[1].
LXE408 (5 mg/kg IV and 20 mg/kg PO) has a T1/2 of 3.3 hours for mouse. LXE408 (3 mg/kg IV and 10 mg/kg PO) has a T1/2 of 3.8 hours, a CL of 2.1 mL/min?kg, and a Vss of 0.53 L/kg for male Sprague-Dawley rat[1].
LXE408 (0.3 mg/kg IV and 1.0 mg/kg PO) has a T1/2 of 3.8 hours for male beagle dog. LXE408 (0.3 mg/kg IV and 10 mg/kg PO) has a T1/2 of 9.7 hours for male cynomolgus monkey[1].
| Animal Model: | Female BALB/c mice (6-8 weeks old) infected with L. donovani[1] | | 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.
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| Animal Model: | Balb/C mice[1] | | Dosage: | 5 mg/kg IV and 20 mg/kg PO (Pharmacokinetic Analysis) | | Administration: | IV or PO | | Result: | Had a T1/2 of 3.3 hours, a CL of 2.3 mL/min?kg, and a Vss of 0.63 L/kg for mouse.
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| [IC 50]
Leishmania | [References]
[1] Advait Nagle, et al. Discovery and Characterization of Clinical Candidate LXE408 as a Kinetoplastid-Selective Proteasome Inhibitor for the Treatment of Leishmaniases. J Med Chem. 2020 Jul 15. DOI:10.1021/acs.jmedchem.0c00499 |
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