ABX-1431

ABX-1431 (1446817-84-0) is a potent (IC50 = 14 nM in vitro, 2.2 nM in human PC3 cells) and very selective (>100-fold over hABHD6, >200-fold over hPLA2G7) inhibitor of monoacylglycerol lipase (MAGL).1 Active in a rat formalin pain test at 3mg/kg. Orally bioavailable and CNS penetrant.

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

Synthesis route for ABX-1431:

[1] JUSTIN S. CISAR. Identification of ABX-1431, a Selective Inhibitor of Monoacylglycerol Lipase and Clinical Candidate for Treatment of Neurological Disorders[J]. Journal of Medicinal Chemistry, 2018, 61 20: 9062-9084. DOI:10.1021/acs.jmedchem.8b00951
[2] Hentsch, Axel, et al. “Highly Specific Miniaturized Fluorescent Monoacylglycerol Lipase Probes Enable Translational Research.” Journal of the American Chemical Society, 2025, pp. 10188–202, https://doi.org/10.1021/jacs.4c15223.
[3] Aida*, Jumpei, et al. “Design, Synthesis, and Evaluation of Piperazinyl Pyrrolidin-2-Ones as a Novel Series of Reversible Monoacylglycerol Lipase Inhibitors.” Journal of Medicinal Chemistry, 61 20, 2018, pp. 9205–17, https://doi.org/10.1021/acs.jmedchem.8b00824.