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| 25mg |
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| Targets |
GPR55 (EC50 = 250 nM)
ML184 targets GPR55, acting as a selective agonist. It activates GPR55, inducing ERK1/2 phosphorylation and promoting PKCβII translocation to the plasma membrane. It also inhibits Aldehyde Dehydrogenase 1 (ALDH1A1) with a potency of 35,481.3 nM and targets the Menin-MLL Interaction. Its primary mechanism is through GPR55 activation. |
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| ln Vitro |
Activation of GPR55 significantly increased proliferation rates of hNSCs in vitro. These effects were attenuated by ML193, a selective GPR55 antagonist. ML184 significantly promoted neuronal differentiation in vitro while ML193 reduced differentiation rates as compared to vehicle treatment. Continuous administration of O-1602 into the hippocampus via a cannula connected to an osmotic pump resulted in increased Ki67+ cells within the dentate gyrus. O-1602 increased immature neuron generation, as assessed by DCX+ and BrdU+ cells, as compared to vehicle-treated animals. GPR55-/- animals displayed reduced rates of proliferation and neurogenesis within the hippocampus while O-1602 had no effect as compared to vehicle controls.[2]
In vitro, ML184 activates GPR55-mediated signaling pathways. It induces ERK1/2 phosphorylation and promotes PKCβII translocation to the plasma membrane. The compound increases proliferation of neural stem cells and promotes neuronal differentiation in vitro. It does not act at the related CB1 or CB2 receptors. |
| ln Vivo |
In vivo, ML184 is used to study the role of GPR55 in cellular proliferation, migration, and inflammatory responses. Its selectivity and efficacy support investigations into GPR55 as a potential therapeutic target. Detailed in vivo efficacy data are limited.
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| Enzyme Assay |
Chemical Library Screening[1]
A β-arrestin (see methods below), high-throughput, high-content screen (HCS) of 300,000 compounds was used here to identify potent GPR55 selective antagonists. This work was performed in collaboration with the Molecular Libraries Probe Production Centers Network program. For more details about this library of compounds, see http://mli.nih.gov/mli/compound-repository/mlsmr-compounds/. Compounds were screened for antagonism (PubChem AID 2026) at GPR55 (using LPI as the agonist), as well as for both agonism and antagonism at GPR35 (PubChem AIDs 2809, 2815), CB1 (PubChem AIDs 2814, 2835) and CB2 (PubChem AIDs 2822, 2836). A cell line permanently expressing a β-arrestin GFP biosensor and an enhanced receptor of interest (i.e., GPR55, GPR35, CB1 or CB2) were employed in the high content imaging assay. Assay protocol descriptions (according to AID number) are accessible at the PubChem website (http://pubchem.ncbi.nlm.nih.gov/). Potent GPR55 antagonist compounds that lacked agonism or antagonism at GPR35, CB1 or CB2, were further evaluated for inhibition of pERK activation and PKCβII translocation produced by the GPR55 agonists, LPI or ML186 (see methods below). A set of novel GPR55 antagonist molecular scaffolds were selected from the screen ML191 (CID23612552), ML192 (CID1434953) and M193(CID1261822), and the binding of each compound was explored using a computer model of the GPR55 inactive state. In vitro assays for ML184 typically measure its binding to and activation of GPR55. Cell lines expressing recombinant GPR55 are treated with the compound, and receptor activation is assessed by measuring GTPγS binding, ERK1/2 phosphorylation, or calcium mobilization. EC50 values are determined from dose-response curves. |
| Cell Assay |
To investigate the effects of GPR55 activation on hNSC proliferation, cells were plated on laminin‐coated 6‐well plates. Cells were allowed to adhere overnight and then treated with LPI (1 μM), the endogenous ligand for GPR55, or synthetic agonists, O‐1602 (1 μM) or ML184 (1 μM), in a reduced growth factor media (5% growth factor). Reduced growth factor medium was utilized to better mimic a less proliferative phenotype while still maintaining a ‘stemness’ state. Analysis by flow cytometry showed no significant reduction of nestin+ or Sox2+ populations after 48 h (data not shown). Cells treated with the selective GPR55 antagonist ML193 (5 μM) were pretreated for 30 min prior to addition of agonist. Vehicle‐treated cells received 0.1% DMSO in 5% growth factor media. For differentiation studies, cells were treated with either vehicle, ML184 (1 μM), ML193 (5 μM), or a combination of ML184 (1 μM) and ML193 (5 μM) in ReNcell medium that did not contain growth factors.[2]
Cellular assays for ML184 are performed using neural stem cells. Cells are treated with the compound, and proliferation is assessed by measuring cell number or by using proliferation assays (e.g., BrdU incorporation). Neuronal differentiation is assessed by measuring the expression of neuronal markers. |
| Animal Protocol |
In vivo animal studies with ML184 are limited, as it is primarily a research compound. When used, it is typically administered to animal models to study the role of GPR55 in various physiological and pathological processes. Detailed dosing regimens and protocols are not widely available.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for ML184 are limited. Its molecular weight is 456.6 g/mol. The compound has a molecular formula of C25H32N4O3S. For research use, it is typically dissolved in DMSO for in vitro studies. Its oral bioavailability and metabolic stability have not been extensively characterized.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for ML184 are limited. In cell-based assays, the compound shows activity at nanomolar concentrations. No significant cytotoxicity has been reported at the doses used for GPR55 activation studies. The compound is intended for laboratory research only and should be handled with standard safety precautions.
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| References |
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| Additional Infomation |
3-[[4-(2,3-dimethylphenyl)-1-piperazinyl]-oxymethyl]-N,N-dimethyl-4-(1-pyrrolidinyl)benzenesulfonamide is a member of the piperazine class of compounds.
ML184 is a research compound used as a selective GPR55 agonist. It is a valuable pharmacological tool for studying GPR55-specific functions, including its role in cellular proliferation, migration, and inflammatory responses. The compound is not approved for clinical use and is intended for laboratory research only. |
| Molecular Formula |
C25H34N4O3S
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|---|---|
| Molecular Weight |
470.63
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| Exact Mass |
470.235
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| Elemental Analysis |
C, 63.80; H, 7.28; N, 11.90; O, 10.20; S, 6.81
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| CAS # |
794572-10-4
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| PubChem CID |
2440433
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
681.4±65.0 °C at 760 mmHg
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| Flash Point |
365.9±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.607
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| LogP |
2.29
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
769
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(N1CCN(C2C(C)=C(C)C=CC=2)CC1)C1C(N2CCCC2)=CC=C(S(N(C)C)(=O)=O)C=1
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| InChi Key |
VRSJAHQGJHDACS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H34N4O3S/c1-19-8-7-9-23(20(19)2)28-14-16-29(17-15-28)25(30)22-18-21(33(31,32)26(3)4)10-11-24(22)27-12-5-6-13-27/h7-11,18H,5-6,12-17H2,1-4H3
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| Chemical Name |
3-[4-(2,3-dimethylphenyl)piperazine-1-carbonyl]-N,N-dimethyl-4-pyrrolidin-1-ylbenzenesulfonamide
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| Synonyms |
ML184; CID 2440433; ML-184; CID-2440433; CID2440433; ML184; 3-[4-(2,3-dimethylphenyl)piperazine-1-carbonyl]-N,N-dimethyl-4-(pyrrolidin-1-yl)benzene-1-sulfonamide; 3-[4-(2,3-dimethylphenyl)piperazine-1-carbonyl]-N,N-dimethyl-4-pyrrolidin-1-ylbenzenesulfonamide; ML-184; MLS001002737; SMR000369190; ML184; CID2440433
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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) |
DMSO: ~12.5 mg/mL (~26.6 mM)
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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 | 2.1248 mL | 10.6241 mL | 21.2481 mL | |
| 5 mM | 0.4250 mL | 2.1248 mL | 4.2496 mL | |
| 10 mM | 0.2125 mL | 1.0624 mL | 2.1248 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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