ABX-1431

SKU: orb1301861

Description

ABX-1431 (Elcubragistat) is a potent, brain-penetrant, and orally bioavailable small molecule inhibitor of monoacylglycerol lipase (MGLL) with an IC50 of 14 nM. It is a valuable research tool for investigating endocannabinoid signaling in preclinical models of neurological disorders, including neuroinflammation and pain.

Research Area

Metabolism Research

Key Properties

• CAS Number: 1446817-84-0
• MW: 507.39
• Purity: 99.27% (May vary between batches)
• Formula: C₂₀H₂₂F₉N₃O₂
• SMILES: FC(F)(F)C(OC(=O)N1CCN(Cc2ccc(cc2N2CCCC2)C(F)(F)F)CC1)C(F)(F)F
• Target: Lipase,MAGL
• Solubility: H2O:Insoluble;Ethanol:10 mg/mL (19.71 mM);10% DMSO+40% PEG300+5% Tween-80+45% Saline:2.5 mg/mL (4.93 mM);DMSO:55 mg/mL (108.4 mM)

Bioactivity

• Target IC50:
  MGLL (human):14 nM|MGLL (mouse):27 nM
• In Vivo:
  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.
• In Vitro:
  ABX-1431 was a potent human MGLL inhibitor (average IC50 = 0.014 μM) with >100-fold selectivity against ABHD6 and >200-fold selectivity against PLA2G7. Treatment of intact human PC3 cells with ABX-1431 following a 30-minute inhibitor incubation time caused concentration-dependent inhibition of MGLL activity with an IC50 value of 0.0022 μM, which is ~6-fold more potent than that observed in vitro. In the cell-based assay, >100-fold selectivity for MGLL over ABHD6 (IC50 = 0.253 μM) and PLA2G7 (IC50 = 494 μM) was maintained.
• Cell Research:
  Human prostate cancer PC3 cells were 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 was added to cells to give final concentration of 0.1–10 μM compound in serum free media. Cells were incubated with compound for 30 min at 37°C with 5% CO2. Cells were washed, harvested, and lysed by probe sonication. Cell lysates (2mg/mL) were treated with JW912 (1μM) and analyzed by SDS-PAGE and in-gel fluorescence scanning.
• Animal Research:
  All animals were 6 8 weeks old at the time of study and weighed between 197-217 g. Animals (n = 3 per dosing route) were dosed with ABX-1431 at 1 mg/kg iv (in 70% polyethylene glycol (PEG) 400 in hydroxypropyl- -cylcodextran (HPBCD) in saline) or 5 mg/kg po (in 70% PEG 400 in 0.5% carboxymethylcellulose (CMC, w/v) in saline). Animals were fasted overnight, and food withheld until 4 h post dose. Approximately 100 μL of blood were collected via a jugular vein catheter at 0.033, 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h after intravenous and 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h after oral administration. All blood samples were collected into tubes containing 400 μL acetonitrile to immediately inactivate blood esterase activity and frozen at 80 °C. Samples were thawed and centrifuged (14,000 rpm for 5 min at 4 °C) and the supernatant transferred for LCMS analysis.

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

MAGL, Inhibitor, Elcubragistat, inhibit, Monoacylglycerol lipase, ABX1431, ABX-1431, ABX 1431

Compound Identifiers

PubChem CID

71657619