ABX-1431

Catalog No.S8823 Batch:S882301

Technical Data

Formula

C₂₀H₂₂F₉N₃O₂

Molecular Weight

507.39

CAS No.

1446817-84-0

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (197.08 mM)

Ethanol

100 mg/mL (197.08 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O

5.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

ABX-1431 is a highly potent, selective, and CNS-penetrant Monoacylglycerol lipase (MGLL) inhibitor with IC50 values of 14 nM and 27 nM for hMGLL and mMGLL respectively.

Targets

hMGLL ^[1]	mMGLL ^[1]
14 nM	27 nM

In vitro

ABX-1431 is 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 min inhibitor incubation time causes 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. ABX-1431 inhibits MGLL via carbamoylation of the catalytic nucleophile Ser122^[1].

In vivo

Pharmacokinetic analysis in rats and dogs of ABX-1431 indicate low to moderate systemic clearance, moderate volume of distribution, and high oral bioavailability (64% in rat, 57% in dog). While ABX-1431 is stable in human and dog plasma, it is not stable in rat plasma. ABX-1431 is a potent and selective inhibitor of MGLL in mouse and rat brain in vivo^[1]. ABX-1431 inhibits MGLL activity with an ED50 of 0.5-1.4 mg/kg (po) and dose-dependently increases brain 2-AG levels in mouse brain. A rat inflammatory pain model is used to assess the pharmacodynamics effect. ABX-1431 demonstrates potent antinociceptive effects in a formalin paw test at a dose that produced near complete MGLL inhibition and maximal elevation of 2-AG^[2].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines PC3 cells Concentrations 0.1-10 μM Incubation Time 30 min Method 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 with compound for 30 min at 37°C with 5% CO2. Cells are washed, harvested, and lysed by probe sonication. Cell lysates (2 mg/mL) are treated with JW912 (1 μM) and analyzed by SDS-PAGE and in-gel fluorescence scanning.
Animal Study:^{^[1]}	Animal Models male Sprague-Dawley rats Dosages 1 mg/kg Administration IV

Cell Assay:^{^[1]}

Cell lines
PC3 cells
Concentrations
0.1-10 μM
Incubation Time
30 min
Method
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 with compound for 30 min at 37°C with 5% CO2. Cells are washed, harvested, and lysed by probe sonication. Cell lysates (2 mg/mL) are treated with JW912 (1 μM) and analyzed by SDS-PAGE and in-gel fluorescence scanning.

Animal Study:^{^[1]}

Animal Models
male Sprague-Dawley rats
Dosages
1 mg/kg
Administration
IV

References

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.