KML29 is an extremely selective, orally active and irreversible MAGL inhibitor, with IC50 values of 15 nM, 43 nM and 5.9 nM for mouse, rat and human MAGL, respectively. KML29 exhibits minimal cross-reactivity toward other central and peripheral serine hydrolases, including no detectable activity against FAAH.
KML29 dose-dependently elevates brain 2-AG level up to 10-fold without alteration in brain levels of anandamide, palmitoylethanolamide, and oleoylethanolamide.
KML29 is a potent inhibitor of 2-AG hydrolysis, but did not affect AEA hydrolysis at any concentration tested.
体内研究
KML29 enhibits antinociceptive activity without cannabimimetic side effects.
KML29 (20 mg/kg) has a significant but modest protective effect against LPS-induced fever.
Animal Model:
C57Bl/6 mice.
Dosage:
1-40 mg/kg.
Administration:
P.O. single dose.
Result:
Selectively inhibited MAGL in mice.
Animal Model:
Wistar albino male rats.
Dosage:
20 mg/kg (+LPS E. coli O111:B4 (250 µg/kg, sc)).
Administration:
SC.
Result:
Administration of KML29 simultaneously with LPS E. coli O111:B4 significantly decreased ∆T (with 5% type 1 error, 1.7 fold) compared to saline+LPS E. coli O111:B4. Administration of KML29 simultaneously with LPS E. coli O111:B4 resulted in decreased plateau phase of fever compared to LPS E. E. coli O111:B4+saline administration.
分子式
C24H21F6NO7
分子量
549.42
CAS号
1380424-42-9
运输条件
Room temperature in continental US; may vary elsewhere.