| Targets |
mAChR3
The primary target of p-F-HHSiD is the M3 subtype of the muscarinic acetylcholine receptor (M3 mAChR). It has been shown to be a selective antagonist for this receptor, allowing researchers to dissect its function from other muscarinic subtypes. It also shows antagonistic properties towards other mAChR subtypes and the alpha1-adrenoceptor. |
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| ln Vitro |
p-F-HHSiD hydrochloride has been shown to block acetylcholine-mediated vasodilation in human umbilical vein endothelial cells (HUVECs). This indicates its direct functional antagonism at M3 mAChRs present on these primary human cells. As a selective antagonist, it is used to study the specific contributions of M3 receptor signaling in various in vitro models, such as smooth muscle contraction and endothelial function.
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| ln Vivo |
No specific in vivo data was found for p-F-HHSiD. However, the compound is described as being used for research on various diseases, including colon cancer, Alzheimer's disease, and diabetes, suggesting its utility as a chemical tool for in vivo target validation. The ability to block M3 mAChRs in vivo helps elucidate the physiological and pathophysiological roles of this receptor in these disease states.
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| Enzyme Assay |
Standard competitive radioligand binding assay: Cell membrane homogenates expressing the human M3 mAChR (1-5 ug protein) are incubated with 0.5 nM [3H]-N-methylscopolamine ([3H]-NMS) and varying concentrations (0.01-10,000 nM) of p-F-HHSiD in 50 mM Tris-HCl buffer (pH 7.4) at 25degC for 2 hours. Non-specific binding is determined in the presence of 1 uM atropine. The reaction is terminated by rapid filtration through GF/B filters, and bound radioactivity is measured by a scintillation counter. Ki values are calculated from IC50 using the Cheng-Prusoff equation.
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| Cell Assay |
A typical cell-based functional assay to measure antagonism: CHO-K1 cells stably expressing human M3 mAChR are seeded in 96-well plates. Cells are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4 AM) for 1 hour at 37degC. The cells are pre-incubated with varying concentrations of p-F-HHSiD (1-1000 nM) for 30 minutes, followed by stimulation with an EC80 concentration of carbachol (a non-specific muscarinic agonist). The intracellular calcium flux is measured using a fluorescence plate reader. The concentration of antagonist required to inhibit 50% of the agonist response is calculated.
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| Animal Protocol |
A general protocol for evaluating M3 antagonists in vivo: Female BALB/c mice are sensitized to ovalbumin (OVA) to induce airway hyperresponsiveness, a model of asthma where M3 receptors are involved in bronchoconstriction. p-F-HHSiD (1, 3, 10 mg/kg) is administered intraperitoneally 30 minutes before an OVA challenge. Airway resistance is measured using whole-body plethysmography (PenH values). The inhibitory effect of the antagonist on bronchoconstriction can then be assessed and compared to a positive control.
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| ADME/Pharmacokinetics |
No specific PK data was found for p-F-HHSiD. As a small-molecule antagonist, it is expected to be well-distributed following parenteral administration. Such compounds typically have a half-life on the order of hours in rodents. Its brain penetration properties are not described, but it is likely designed for both peripheral and potentially central nervous system applications.
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| Toxicity/Toxicokinetics |
No toxicity data was found for p-F-HHSiD. As a research chemical, it should be handled with standard laboratory safety precautions. The detailed safety profile is not available, but based on its mechanism as a muscarinic antagonist, high systemic doses could lead to side effects such as dry mouth, blurred vision, and tachycardia.
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| References |
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| Additional Infomation |
p-F-HHSiD hydrochloride is a research-grade chemical supplied for laboratory use only, not for human therapeutic applications. Its CAS number is 175615-76-6, molecular formula C20H33ClFNOSi, and molecular weight 386.02. It is a valuable tool for studying the M3 mAChR in a wide range of research areas, including cancer, metabolic, neurological, and cardiovascular diseases. This product is not for clinical or diagnostic use. Each product in one row, fields tab-separated.
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| CAS # |
175615-76-6
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|---|---|
| Related CAS # |
116679-83-5
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| Appearance |
Solid powder
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| Synonyms |
p-Fluorohexahydrosiladifenidol hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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.) |
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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