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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
ABX-1431 is a highly potent, selective, covalent, irreversible, and orally bioavailable, CNS-penetrant MGLL (serine hydrolase monoacylglycerol lipase) inhibitor that has potential use in the treatment of neurological disorders. Monoacylglycerol lipase (MGLL or MAGL) is a critical point of regulation of both endocannabinoid and eicosanoid signaling pathways in the brain, thereby providing novel therapeutic opportunities for neurological and neurodegenerative diseases. Activity-based protein profiling experiments verify the exquisite selectivity of ABX-1431 for MGLL versus other members of the serine hydrolase class. 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. ABX-1431 is currently under evaluation in human clinical trials.
| ln Vitro |
Elcubragistat, also known as ABX-1431, is a highly effective human MGLL inhibitor (IC50=0.014 µM) that exhibits selectivity levels of >200 against PLA2G7 and >100 against ABHD6. Elcubragistat has an IC50 of 0.0022 µM for inhibiting human PC3 cells. >100-fold selectivity for MGLL over PLA2G7 (IC50=494 µM) and ABHD6 (IC50=0.253 µM) is maintained in the cell-based assay[1].
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| ln Vivo |
Elcubragistat (ABX-1431) raises brain 2-AG concentrations, reduces pain behavior in the rat formalin pain paradigm, and inhibits MGLL activity in rodent brains (ED50=0.5-1.4 mg/kg)[1].
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| Additional Infomation |
ABX-1431 is under investigation in clinical trial NCT03625453 (Study of ABX-1431 in Adult Patients With Tourette Syndrome or Chronic Motor Tic Disorder).
Elcubragistat is an orally bioavailable inhibitor of the serine hydrolase monoacylglycerol lipase (MGLL), with potential use for the treatment of various central nervous system (CNS) diseases and with potential analgesic and anti-neuroinflammatory activities. Upon oral administration, elcubragistat targets and binds to MGLL, thereby inhibiting MGLL activity and preventing the breakdown and inactivation of endogenous 2-arachidonoylglycerol (2-AG). Increased 2-AG levels results in enhanced activation of the cannabinoid receptor 1 (CB1) in the CNS and enhanced CB1 endocannabinoid signaling in active neural circuits. Activation of CB1 helps modulate the endocannabinoid system and reduce neurotransmitter release, thereby decreasing overactive neural signaling. This induces analgesic, anti-inflammatory and various neurological effects that are caused by dysregulation of the endocannabinoid system and overactive neural signaling, including anxiolytic effects, reduced spasticity and decreased neurodegenerative effects. In addition, MGLL inhibition by elcubragistat depletes the supply of the inflammatory signaling molecule arachidonic acid, thereby further alleviating pain and inflammation. CB1 plays a key role in the regulation of neurotransmission; increased CB1 activation decreases overactive neural signaling. MGLL, an enzyme that catalyzes the breakdown of 2-AG, regulates the activation of CB1 and CB2 to modulate neurotransmission and inflammatory signaling, respectively. |
| Molecular Formula |
C20H22F9N3O2
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| Molecular Weight |
507.39
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| Exact Mass |
507.156
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| CAS # |
1446817-84-0
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| Related CAS # |
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| PubChem CID |
71657619
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| Appearance |
White to light yellow solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
34
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| Complexity |
670
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(C2C=C(C(F)(F)F)C=CC=2CN2CCN(C(OC(C(F)(F)F)C(F)(F)F)=O)CC2)CCCC1
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| InChi Key |
SQZJGTOZFRNWCX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22F9N3O2/c21-18(22,23)14-4-3-13(15(11-14)31-5-1-2-6-31)12-30-7-9-32(10-8-30)17(33)34-16(19(24,25)26)20(27,28)29/h3-4,11,16H,1-2,5-10,12H2
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| Chemical Name |
1,1,1,3,3,3-hexafluoropropan-2-yl 4-[[2-pyrrolidin-1-yl-4-(trifluoromethyl)phenyl]methyl]piperazine-1-carboxylate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (4.10 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9709 mL | 9.8544 mL | 19.7087 mL | |
| 5 mM | 0.3942 mL | 1.9709 mL | 3.9417 mL | |
| 10 mM | 0.1971 mL | 0.9854 mL | 1.9709 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 J Med Chem.2018 Oct 25;61(20):9059-9061. |
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 J Med Chem.2018 Oct 25;61(20):9062-9084. |
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