LEI-401 (C09-1142-351)

LEI-401 is a first-in-class, selective, and CNS-active NAPE-PLD (N-acylphosphatidylethanolamine phospholipase D) inhibitor, with an IC 50 of 27 nM. LEI-401 modulates emotional behavior in mice.In VitroLEI-401 reduced a broad range of NAEs including anandamide in neuronal cells in a NAPE-PLD-dependent manner. LEI-401 (0.04-20 μM; 30 minutes) dose-dependently reduces the labeling of NAPE-PLD with an IC 50 of 0.86 μM in hNAPE-PLD-transfected HEK293T cells. LEI-401 reduces NAE levels in Neuro-2a cells, but not in NAPE-PLD KO cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoLEI-401 (30 mg/kg; i.p.) diminishes fear extinction in mice . LEI-401 also activates HPA axis signaling . LEI-401 (10 mg/kg; p.o.) treatment shows the t 1/2 , C max , t max , AUC last , and F values of 2.5 hours, 1370 ng/mL, 2 hours, 6760 h*ng/mL, and 25%, respectively . LEI-401 (30 mg/kg; i.p.) treatment show the C max , t max , AUC last , and F values of 10300 ng/mL, 1 hour, 38600 h*ng/mL, and 48%, respectively . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male 7–12-week-old C57BL/6J mice Dosage: 30 mg/kg Administration: I.p. Result: Produced a significant increase in freezing as compared to vehicle. Animal Model: C57BL/6J mice Dosage: 10 mg/kg Administration: P.o. (Pharmacokinetic Analysis) Result: The t 1/2 , C max , t max , AUC last , and F values were 2.5 hours, 1370 ng/mL, 2 hours, 6760 h*ng/mL, and 25%, respectively.Form:Solid. Specification: 0.99 Molecular Formula: C24H31N5O2 Molecular Weight: 421.54 PubChem CID: 145998143 Isomeric SMILES: C1C[C@H](CN(C1)C2=NC(=CC(=N2)N3CC[C@@H](C3)O)C(=O)NCC4CC4)C5=CC=CC=C5