MAGL-IN-1 is a specific, reversible and competitive MAGL inhibitor (antagonist) with IC50 of 80 nM. MAGL-IN-1 has antiproliferation effects on human breast, colorectal, and ovarian cancer cells. MAGL-IN-1 blocks MAGL both in vivo and in vitro.

Physicochemical Properties

Molecular Formula	C22H24FNO3
Molecular Weight	369.43
Exact Mass	369.174
CAS #	2324160-91-8
PubChem CID	138319671
Appearance	White to off-white solid powder
Density	1.2±0.1 g/cm3
Boiling Point	558.9±50.0 °C at 760 mmHg
Flash Point	291.8±30.1 °C
Vapour Pressure	0.0±1.6 mmHg at 25°C
Index of Refraction	1.585
LogP	3.17
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	522
Defined Atom Stereocenter Count	0
InChi Key	WUUBZNFATQKRPH-UHFFFAOYSA-N
InChi Code	InChI=1S/C22H24FNO3/c1-14(2)15-3-5-16(6-4-15)21(26)17-9-11-24(12-10-17)22(27)19-13-18(25)7-8-20(19)23/h3-8,13-14,17,25H,9-12H2,1-2H3
Chemical Name	[1-(2-fluoro-5-hydroxybenzoyl)piperidin-4-yl]-(4-propan-2-ylphenyl)methanone
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: 80 nM (MAGL)[1]
ln Vitro	In all examined cancer cell lines, MAGL-IN-1 (Compound 23) (0.02 - 200 μM; 96 hours) significantly inhibits cell viability, with an IC50 ranging from 7.9 to 57 μM [1]. Using 4-nitrobenzene acetate, MAGL-IN-1 (0.125-1 μM; 30 minutes) binds MAGL in a competitive manner with a Ki of 39 nM [1]. At 10 μM, MAGL-IN-1 (10 μM; 90 min) [1]. In U937 cells, MAGL-IN-1 (1 nM-100 μM; 15 min) inhibits [3H]2-oleoylglycerol (2-OG) hydrolysis in a concentration-dependent manner with an IC50 of 193 nM [1]. With an IC50 of 2.1 μM, MAGL-IN-1 (0.01-30 μM; 15 min) inhibits 2-OG hydrolysis in mouse meningeal preparations in a concentration-dependent manner [1].
ln Vivo	In mouse plasma and brain levels, MAGL (Compound 23) (50 mg/kg; single ip) raises 2-AG levels without changing levels of AEA, arachidonic acid, or prostate[1].
Cell Assay	Cell Proliferation Assay[1] Cell Types: HCT116, MDA-MB-231, CAOV3, OVCAR3, SKOV3, and MRC5 cells Tested Concentrations: 0.02-200 μM Incubation Duration: 96 hrs (hours) Experimental Results: Inhibited the growth of human breast MDA-MB-231 , colorectal HCT116, and ovarian CAOV3, OVCAR3, and SKOV3 cancer cells, with IC50s of 7.9, 21, 25, 57, and 15 μM, respectively. Was inactive against MRC5 (IC50>100 μM).
Animal Protocol	Animal/Disease Models: Male C57BL6 mice, 8-10 weeks old[1] Doses: 50 mg/kg Route of Administration: intraperitoneal (ip) injection; once Experimental Results: Increased 2-AG levels in the brain and plasma.
References	[1]. Optimization of a Benzoylpiperidine Class Identifies a Highly Potent and Selective Reversible Monoacylglycerol Lipase (MAGL) Inhibitor. J Med Chem. 2019 Feb 28;62(4):1932-1958.

Solubility Data

Solubility (In Vitro)

DMSO: 62.5 mg/mL (169.18 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.08 mg/mL (5.63 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (5.63 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7069 mL	13.5344 mL	27.0687 mL
	5 mM	0.5414 mL	2.7069 mL	5.4137 mL
	10 mM	0.2707 mL	1.3534 mL	2.7069 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.