| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CB1[1]
Monlunabant targets the cannabinoid receptor type 1 (CB1) and, to a lesser extent, cannabinoid receptor type 2 (CB2). It is a peripherally acting inverse agonist of CB1R. The compound inhibits CB1-induced β-arrestin-2 recruitment with an IC50 of 21 pM and inhibits G protein activation with an IC50 of 6 nM. Its high selectivity for CB1 (Ki = 0.3 nM) over CB2 (Ki = 613 nM) indicates that it is approximately 2000-fold selective for CB1. |
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| ln Vitro |
In vitro, Monlunabant inhibits CB1-induced β-arrestin-2 recruitment with an IC50 of 21 pM and inhibits G protein activation with an IC50 of 6 nM. At concentrations of 0.3-30 nM for 60 minutes, the compound enhances insulin secretion in INS-1 (832/13) cells, as well as human and mouse islet cells in the presence of 10 mM glucose. At 3 nM for 48 hours, Monlunabant inhibits cytokine-induced apoptosis in human islets. These in vitro studies demonstrate the compound's CB1 antagonist activity and its potential metabolic benefits.
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| ln Vivo |
In vivo, Monlunabant has been studied in animal models for its effects on metabolism and cannabinoid receptor signaling. As a peripherally acting CB1 inverse agonist, it is designed to block CB1 receptors in peripheral tissues while minimizing central nervous system side effects. The compound has shown potential for treating metabolic disorders and their complications. However, detailed in vivo efficacy data from published literature are limited. The compound is administered orally and has demonstrated activity in preclinical models of metabolic disease.
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| Enzyme Assay |
For non-cell-based receptor binding assays, Monlunabant can be evaluated using membrane preparations from cells expressing human CB1 or CB2 receptors. Radioligand binding displacement experiments are performed using [3H]-CP55940 as the radiolabeled ligand. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand at 30°C for 60 minutes. Bound radioligand is separated from free by filtration through GF/B filters. Nonspecific binding is determined in the presence of 10 µM unlabeled CP55940. Ki values are calculated from displacement curves using nonlinear regression analysis.
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| Cell Assay |
For in vitro cellular assays, cells expressing human CB1 or CB2 receptors (e.g., CHO or HEK293 cells) are cultured in appropriate media. For β-arrestin-2 recruitment assays, cells are transfected with CB1 receptor and β-arrestin-2 fusion proteins. After treatment with various concentrations of Monlunabant, β-arrestin-2 recruitment is measured using BRET or enzyme complementation technology. For G protein activation assays, [35S]GTPγS binding is measured. For insulin secretion assays, INS-1 cells or isolated islets are treated with the compound and glucose-stimulated insulin secretion is measured by ELISA.
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| Animal Protocol |
For in vivo animal studies, Monlunabant is typically administered orally to rodents. In metabolic disease models (e.g., diet-induced obesity or diabetes models), body weight, food intake, glucose tolerance, and insulin sensitivity are measured. In models of respiratory complications, lung function and inflammatory markers are assessed. In models of renal complications, kidney function and fibrosis markers are evaluated. Dosing regimens vary depending on the specific model. Blood and tissue samples are collected for pharmacokinetic and pharmacodynamic analysis.
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| ADME/Pharmacokinetics |
Monlunabant is an orally active compound. As a solid dispersion formulation, it is designed to improve oral bioavailability. The compound has a molecular weight that allows for good absorption and distribution. Its peripheral restriction is designed to minimize central nervous system penetration and associated side effects. The compound is available in DMSO solution for research use. Comprehensive pharmacokinetic studies would include assessment of oral bioavailability, half-life, protein binding, and tissue distribution.
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| Toxicity/Toxicokinetics |
The toxicity profile of Monlunabant has not been extensively published. As a CB1 inverse agonist, potential adverse effects may include those associated with CB1 receptor blockade, such as gastrointestinal disturbances, mood changes, and anxiety. The compound is designed to be peripherally acting to minimize central nervous system side effects. The compound is for research use only and not for human consumption. Standard toxicological evaluation would include acute and repeated-dose toxicity studies, genotoxicity assessment, and cardiovascular safety pharmacology.
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| References | |
| Additional Infomation |
Monlunabant ((S)-MRI-1891, INV-202) is a peripherally acting CB1 receptor inverse agonist being developed for the treatment of metabolic disorders and their complications. It binds to hCB1 with high affinity (Ki = 0.3 nM) and shows approximately 2000-fold selectivity over hCB2 (Ki = 613 nM). The compound is a solid dispersion formulation that is orally active. It is being investigated for potential applications in respiratory and renal complications associated with metabolic disorders. The compound is for research use only and has not been approved for clinical use.
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| Molecular Formula |
C26H22CLF3N6O3S
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|---|---|
| Molecular Weight |
591.004493236542
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| Exact Mass |
590.111
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| Elemental Analysis |
C, 52.84; H, 3.75; Cl, 6.00; F, 9.64; N, 14.22; O, 8.12; S, 5.42
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| CAS # |
2712480-46-9
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| Related CAS # |
(R)-Monlunabant;2765579-76-6; 1610420-66-0 (racemic); 2712480-46-9 (S-isomer); 2244778-08-1
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| PubChem CID |
164888943
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| Appearance |
White to off-white solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
40
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| Complexity |
1100
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(=O)N/C(=N/C(=N/S(=O)(=O)C1=CC=C(C=C1)C(F)(F)F)/N2C[C@@H](C(=N2)C3=CC=C(C=C3)Cl)C4=CC=CC=C4)/N
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| InChi Key |
GYJPQNPVIJXXTA-JOCHJYFZSA-N
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| InChi Code |
InChI=1S/C26H22ClF3N6O3S/c1-16(37)32-24(31)33-25(35-40(38,39)21-13-9-19(10-14-21)26(28,29)30)36-15-22(17-5-3-2-4-6-17)23(34-36)18-7-11-20(27)12-8-18/h2-14,22H,15H2,1H3,(H3,31,32,33,35,37)/t22-/m1/s1
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| Chemical Name |
N-[(E)-N'-[(Z)-C-[(4S)-5-(4-chlorophenyl)-4-phenyl-3,4-dihydropyrazol-2-yl]-N-[4-(trifluoromethyl)phenyl]sulfonylcarbonimidoyl]carbamimidoyl]acetamide
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| Synonyms |
Monlunabant; 2712480-46-9; MRI-1891; INV-202; MRI1891; S-MRI-1891; INV 202; INV202; (-)-MRI-1891; MRI-1,891; MRI 1891; RefChem:1089808; 4G8X27X87A;
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6920 mL | 8.4602 mL | 16.9205 mL | |
| 5 mM | 0.3384 mL | 1.6920 mL | 3.3841 mL | |
| 10 mM | 0.1692 mL | 0.8460 mL | 1.6920 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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