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ABX-1431

Names

[ CAS No. ]:
1446817-84-0

[ Name ]:
ABX-1431

Biological Activity

[Description]:

ABX-1431 is a highly potent, selective, and orally available, CNS-penetrant monoacylglycerol lipase (MAGL) inhibitor with an IC50 of 14 nM.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> MAGL
Research Areas >> Neurological Disease

[Target]

IC50: 14 nM (human MGLL)[1]


[In Vitro]

ABX-1431 is a potent human MGLL inhibitor (IC50=0.014 µM) with >100-fold selectivity against ABHD6 and >200-fold selectivity against PLA2G7. ABX-1431 inhibits human PC3 cells with an IC50 of 0.0022 µM. In the cell-based assay, >100-fold selectivity for MGLL over ABHD6 (IC50=0.253 µM) and PLA2G7 (IC50=494 µM) is maintained[1].

[In Vivo]

ABX-1431 inhibits MGLL activity in rodent brain (ED50=0.5-1.4 mg/kg), increases brain 2-AG concentrations, and suppresses pain behavior in the rat formalin pain model[1].

[Cell Assay]

Human prostate cancer PC3 cells are grown in F-12K medium supplemented with 10% fetal bovine serum at 37°C with 5% CO2 to 80% confluency in 100 mm dishes. ABX-1431 is added to cells to give final concentration of 0.1-10 µM compound in serum free media. Cells are incubated for 30 min. Cells are washed, harvested, and lysed by probe sonication. Cell lysates (2mg/mL) are treated with JW912 (1µM) and analyzed by SDS-PAGE and in-gel fluorescence scanning[1].

[Animal admin]

Rats[1] ABX-1431 is administered in a volume of 5 mL/kg. Male ICR mice or male Sprague Dawley rats 6 to 12 weeks are administered single oral doses of ABX-1431 (0.5-32 mg/kg for mice and 0.03-10 mg/kg for rats). Four hours after ABX-1431 administration, animals are anesthetized. Following blood collection, animals are killed by decapitation and brains are removed, hemisected and frozen in liquid nitrogen for analysis[1].

[References]

[1]. Cisar JS, et al. Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorders. J Med Chem. 2018 Oct 25;61(20):9062-9084.


[Related Small Molecules]

JZL184 | JZL195 | WWL 70 | KML 29 | JW 642 | JJKK 048

Chemical & Physical Properties

[ Molecular Formula ]:
C20H22F9N3O2

[ Molecular Weight ]:
507.39

[ Storage condition ]:
2-8℃


Related Compounds