LEI-401

• CAT Number: I015142
• CAS Number: 2393840-15-6
• Molecular Formula: C24H31N5O2
• Molecular Weight: 421.54
• Purity: ≥95%
• Synonyms: N-(cyclopropylmethyl)-6-[(3S)-3-hydroxypyrrolidin-1-yl]-2-[(3S)-3-phenylpiperidin-1-yl]pyrimidine-4-carboxamide
• InChI: InChI=1S/C24H31N5O2/c30-20-10-12-28(16-20)22-13-21(23(31)25-14-17-8-9-17)26-24(27-22)29-11-4-7-19(15-29)18-5-2-1-3-6-18/h1-3,5-6,13,17,19-20,30H,4,7-12,14-16H2,(H,25,31)/t19-,20+/m1/s1
• InChIKey: GFHJYPQZBBHOCC-UXHICEINSA-N
• SMILES: C1CC(CN(C1)C2=NC(=CC(=N2)N3CCC(C3)O)C(=O)NCC4CC4)C5=CC=CC=C5

LEI-401 is a first-in-class, selective, and CNS-active NAPE-PLD (N-acylphosphatidylethanolamine phospholipase D) inhibitor, with an IC50 of 27 nM. LEI-401 modulates emotional behavior in mice[1].
LEI-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 IC50 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[1].
LEI-401 (30 mg/kg; i.p.) diminishes fear extinction in mice[1].
LEI-401 also activates HPA axis signaling[1].
LEI-401 (10 mg/kg; p.o.) treatment shows the t1/2, Cmax, tmax, AUClast, and F values of 2.5 hours, 1370 ng/mL, 2 hours, 6760 h*ng/mL, and 25%, respectively[1].
LEI-401 (30 mg/kg; i.p.) treatment show the Cmax, tmax, AUClast, and F values of 10300 ng/mL, 1 hour, 38600 h*ng/mL, and 48%, respectively[1].

Reference

[1]. Mock ED, et al. Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice. Nat Chem Biol. 2020;16(6):667-675.
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