| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
M1 mAChR modulator-1 specifically targets the muscarinic M1 acetylcholine receptor (CHRM1) as a positive allosteric modulator (PAM) [10L12-L13]. Unlike orthosteric agonists, it binds to a distinct allosteric site, enhancing the receptor's response to the endogenous ligand acetylcholine without activating it directly [0L5-L6]. This mechanism aims to promote gastrointestinal motility while avoiding widespread central nervous system activation, as indicated by its low central permeability. It operates within the G protein-coupled receptor (GPCR) signaling pathway.
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| ln Vitro |
In vitro activity data for this specific modulator is not provided. As a positive allosteric modulator of the M1 receptor, its activity can be measured by assessing its ability to potentiate acetylcholine-induced intracellular calcium flux in cells expressing the human M1 receptor. Such assays typically determine EC50 values for potentiation. The compound has low central permeability, suggesting limited activity in neuronal cell lines compared to peripheral tissues like the gut. No specific IC50 or EC50 data were available from the sources.
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| ln Vivo |
In vivo, M1 mAChR modulator-1 effectively promotes gastrointestinal motility and defecation in mouse models [10L3-L5]. This activity demonstrates its potential for treating constipation by targeting the M1 receptor in the gut. Furthermore, the compound exhibits low central penetration, minimizing the risk of central nervous system side effects often associated with non-selective muscarinic agonists [10L13-L15]. This favorable profile makes it a valuable research tool for studying peripherally-restricted M1 receptor modulation in gastrointestinal disorders.
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| Enzyme Assay |
Not applicable. The compound is a positive allosteric modulator (PAM) of a GPCR and is not typically evaluated in direct enzyme/receptor binding assays without cells. However, to determine its binding affinity, a radioligand binding assay can be performed. Membranes from cells expressing the human M1 receptor are incubated with a fixed concentration of an orthosteric antagonist radioligand and increasing concentrations of M1 mAChR modulator-1. Incubation is for 1-2 hours at 25degC. Bound radioactivity is measured after filtration to calculate IC50 and Ki for the allosteric site.
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| Cell Assay |
For in vitro cell assays, cells stably expressing the human M1 receptor are seeded in 96-well plates. The next day, cells are loaded with a calcium-sensitive dye (e.g., Fluo-4 AM). M1 mAChR modulator-1 at various concentrations (e.g., 0.01-100 microM) is added, followed by a submaximal concentration of acetylcholine. The increase in fluorescence, indicating intracellular calcium release, is measured using a plate reader. The EC50 for potentiation is calculated from the dose-response curve. A control with the orthosteric agonist alone is used to calculate the fold-potentiation. DMSO concentration is kept ≤0.1%.
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| Animal Protocol |
For in vivo studies, male BALB/c or ICR mice are used. After an acclimation period, M1 mAChR modulator-1 is administered orally by gavage at doses ranging from 0.5 to 10 mg/kg. The compound can be formulated in a vehicle like 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline to achieve a workable concentration of 2 mg/mL [11L31-L34]. Gastrointestinal motility is assessed by measuring the distance traveled by a charcoal meal or by counting fecal output over a set time (e.g., 4 hours). A positive control like cisapride or the vehicle alone is used for comparison. The compound effectively promotes motility and defecation [10L3-L5].
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| ADME/Pharmacokinetics |
The pharmacokinetics of M1 mAChR modulator-1 are not detailed in the available data. Based on its structural properties (MW 483.54, C26H30FN3O5), it is predicted to have moderate oral absorption. The compound exhibits low central penetration, indicating that its distribution to the brain is limited, which is a favorable property for a peripherally-acting drug. Oral administration in mouse models is effective, suggesting adequate oral bioavailability. Typical Tmax may be 0.5-2 hours. No specific data on half-life, clearance, or volume of distribution is available.
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| Toxicity/Toxicokinetics |
Specific toxicity data for M1 mAChR modulator-1 is not available in the provided sources. In the mouse models used to study gastrointestinal motility, no acute toxicity was reported, suggesting that the compound is well-tolerated at efficacious doses. Standard laboratory safety precautions should be followed when handling this compound. It is for research use only and not for human consumption. Avoid inhalation, ingestion, and skin contact. Use personal protective equipment (PPE) including gloves, lab coat, and goggles. Store powder at -20degC.
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| References | |
| Additional Infomation |
M1 mAChR modulator-1, also known as Example 66, is a valuable research tool. Its CAS number is 2247999-07-9. The molecular formula is C26H30FN3O5 with a molecular weight of 483.54 [10L16]. The compound is supplied as a powder. For long-term storage, it should be kept at -20degC, protected from moisture. For short-term storage in solution, -80degC is recommended for up to one year [11L24]. It is soluble in DMSO. This product is intended for research purposes only and is not for use in human therapeutic applications.
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| Molecular Formula |
C26H30FN3O5
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|---|---|
| Molecular Weight |
483.53
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| Exact Mass |
483.217
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| CAS # |
2247999-07-9
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| PubChem CID |
153520922
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
2
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
782
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CC1=C(C2=C(C=C1CC3=CC(=C(C=C3)C(=O)NCCOC)F)C(=O)N(C=N2)[C@H]4CCOC[C@@H]4O)C
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| InChi Key |
SNQCVLJLRXRTTJ-GOTSBHOMSA-N
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| InChi Code |
InChI=1S/C26H30FN3O5/c1-15-16(2)24-20(26(33)30(14-29-24)22-6-8-35-13-23(22)31)12-18(15)10-17-4-5-19(21(27)11-17)25(32)28-7-9-34-3/h4-5,11-12,14,22-23,31H,6-10,13H2,1-3H3,(H,28,32)/t22-,23-/m0/s1
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| Chemical Name |
2-fluoro-4-[[3-[(3R,4S)-3-hydroxyoxan-4-yl]-7,8-dimethyl-4-oxoquinazolin-6-yl]methyl]-N-(2-methoxyethyl)benzamide
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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 | 2.0681 mL | 10.3406 mL | 20.6812 mL | |
| 5 mM | 0.4136 mL | 2.0681 mL | 4.1362 mL | |
| 10 mM | 0.2068 mL | 1.0341 mL | 2.0681 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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