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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
BML-190 (formerly IMMA; LM-4131; BML-190; LM4131; BML190; Indomethacin morpholinylamide), is a potent and selective cannabinoid CB2 receptor inverse agonist with potential anti-inflammatory activity. It exhibits 50-fold selectivity over the CB1 receptor and activates the cannabinoid CB2 receptor with a Ki of 435 nM.
| Targets |
CB2 ( Ki = 435 nM )
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| ln Vitro |
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| Enzyme Assay |
The aminoalkylindole BML-190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB(2) and CB(1) receptors, respectively. In HEK-293 cells stably expressing the human CB(2) receptor, BML-190 and AM251 potentiated the forskolin-stimulated accumulation of cAMP. Moreover, the CB(2) receptor can interact productively with 16z44, a promiscuous G alpha(16/z) chimera. BML-190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB(2) receptor and 16z44. These results demonstrate that BML-190 and AM251 act as inverse agonists at the human CB(2) receptor acting via G alpha(i/o) and G alpha(q) family-coupled pathways.[1]
Stock solutions of 15 mM BML-190 were prepared in DMSO and added in 2-µL aliquots as substrate to individual incubation aliquots. Rat liver microsomes containing 1.5 mg/mL of protein concentration were pre-incubated at 37 °C for 30 min. The 0.4-mL incubation aliquots contained 90 mM potassium phosphate (pH 7.4), 17 mM magnesium chloride, 7 mM NADPH, 17 mM glucose-6-phosphate, and 1.2 units of glucose-6-phosphate dehydrogenase. Incubation times ranged from 0.5 to 4 h. Incubations were halted by placing the incubation vials in an ice bath followed by the addition of an equal volume of methanol (0.2 mL). The quenched incubation mixtures were stored at −20 °C until analysis. Prior to HPLC separation, microsomal proteins were precipitated by centrifugation at room temperature, and the solvent was evaporated with a stream of nitrogen at 37 °C. The residual solution was applied to 6-mL SUPELCO C18 solid-phase extraction (SPE) columns pre-treated with water and methanol. The columns were washed with HPLC-grade water followed by elution with methanol. The effluents were again concentrated by a nitrogen stream at 37 °C to near dryness before reconstitution with methanol to 1 mL volumes for HPLC analysis.[2] |
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| Cell Assay |
For 20 to 24 hours, 293/CB2 cells are labeled with [3H]adenine (1 μCi/mL) in MEM containing 1% FBS. After 30 minutes at 37°C, labeled cells are challenged with 50 μM forskolin and the relevant BML-190, and the accumulation of cAMP is measured. Using transfection reagents, 2 × 105 293/CB2 cells are transiently transfected with 16z44 and/or pcDNA3 for IP assays. In order to produce IP, cells are labeled, challenged with BML-190, and assayed. For every data point, triplicates are run, and each ligand is tested in at least three different trials.
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| Animal Protocol |
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| References | |||
| Additional Infomation |
Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) is the major psychoactive component of marijuana and elicits pharmacological actions via cannabinoid receptors. Anandamide (AEA) and 2-arachidonoyl-glycerol (2-AG) are endogenous ligands for cannabinoid receptors, which because of their structural similarities to arachidonic acid (AA), AEA, and 2-AG could serve as substrates for lipoxygenases and cyclooxygenases (COXs) that metabolize polyunsaturated fatty acids to potent bioactive molecules. In this study, we have compared the effects of Delta(9)-THC, AEA, 2-AG, and another cannabinoid agonist, indomethacin morpholinylamide (IMMA), on lipopolysaccharide (LPS)-induced NO, IL-6, and PGE(2) release from J774 macrophages. Delta(9)-THC, IMMA, and AEA diminish LPS-induced NO and IL-6 production in a concentration-dependent manner. 2-AG inhibits the production of IL-6 but slightly increases iNOS-dependent NO production. Delta(9)-THC and IMMA also inhibit LPS-induced PGE(2) production and COX-2 induction, while AEA and 2-AG have no effects. These discrepant results of 2-AG on iNOS and COX-2 induction might be due to its bioactive metabolites, AA and PGE(2), whose incubation cause the potentiation of both iNOS and COX-2 induction. On the contrary, the AEA metabolite, PGE(2)-ethanolamide, influences neither the LPS-induced NO nor IL-6 production. Taken together, direct cannabinoid receptor activation leads to anti-inflammatory action via inhibition of macrophage function. The endogenous cannabinoid, 2-AG, also serves as a substrate for COX-catalyzing PGE(2) production, which in turn modulates the action of CB2.[3]
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| Molecular Formula |
C23H23CLN2O4
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| Molecular Weight |
426.89
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| Exact Mass |
426.134
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| Elemental Analysis |
C, 64.71; H, 5.43; Cl, 8.30; N, 6.56; O, 14.99
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| CAS # |
2854-32-2
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| Related CAS # |
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| PubChem CID |
2415
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
586.7±50.0 °C at 760 mmHg
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| Flash Point |
308.6±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.625
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| LogP |
2.99
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| SMILES |
CC(N1C(C2=CC=C(Cl)C=C2)=O)=C(CC(N3CCOCC3)=O)C4=C1C=CC(OC)=C4
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| InChi Key |
BJSDNVVWJYDOLK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H23ClN2O4/c1-15-19(14-22(27)25-9-11-30-12-10-25)20-13-18(29-2)7-8-21(20)26(15)23(28)16-3-5-17(24)6-4-16/h3-8,13H,9-12,14H2,1-2H3
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| Chemical Name |
2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-1-morpholin-4-ylethanone
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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: ≥ 2.5 mg/mL (5.86 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 25.0 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 | 2.3425 mL | 11.7126 mL | 23.4252 mL | |
| 5 mM | 0.4685 mL | 2.3425 mL | 4.6850 mL | |
| 10 mM | 0.2343 mL | 1.1713 mL | 2.3425 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.
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