LXE408 fumarate是一种口服有效的，非竞争性的，动素体选择性Proteasome" style="display: inline; color: #c13a36">蛋白酶体 (Proteasome) 抑制剂。LXE408 fumarate抑制 L. donovani Proteasome" style="display: inline; color: #c13a36">蛋白酶体 (IC50=0.04 μM) 和 L. donovani (EC50=0.04 μM)。LXE408 fumarate具有较弱的透过血脑屏障能力。LXE408 fumarate具有用于内脏利什曼病 (VL) 研究的潜力。

LXE408 fumarate is an orally active, non-competitive and kinetoplastid-selective proteasome inhibitor. LXE408 fumarate has an IC50 of 0.04 μM for L. donovani proteasome and an EC50 of 0.04 μM for L. donovani. LXE408 fumarate has a low propensity to cross the blood brain barrier. LXE408 fumarate has the potential for visceral leishmaniasis (VL) research.

LXE408 fumarate occupy the pocket as a ternary complex with the proteasome. In a manual patch clamp assay, LXE408 fumarate shows no inhibition of the hERG channel (IC50>30 μM). LXE408 fumarate has a low propensity to cross the blood brain barrier (brain/plasma AUC ratio=0.03 in mice)[1].

LXE408 fumarate ( 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 fumarate (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 fumarate (5 mg/kg IV and 20 mg/kg PO) has a T1/2 of 3.3 hours for mouse. LXE408 fumarate (3 mg/kg IV and 10 mg/kg PO) has a T1/2 of 3.8 hours, a CL of 2.1 mL/minokg, and a Vss of 0.53 L/kg for male Sprague-Dawley rat. LXE408 fumarate (0.3 mg/kg IV and 1.0 mg/kg PO) has a T1/2 of 3.8 hours for male beagle dog. LXE408 fumarate (0.3 mg/kg IV and 10 mg/kg PO) has a T1/2 of 9.7 hours for male cynomolgus monkey[1].

C27H22FN7O6

559.51

LXE408 fumarate (1799330-15-6 Free base)

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years