| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
The primary molecular target of 7-Hydroxygranisetron is the serotonin 5-HT3 receptor, a ligand-gated ion channel. As a major metabolite of Granisetron, it acts as a 5-HT3 receptor antagonist. Granisetron and its metabolite block serotonin from binding to 5-HT3 receptors located both centrally in the medullary chemoreceptor trigger zone (CTZ) and peripherally in the gastrointestinal tract. This antagonism disrupts serotonin-dependent signaling pathways, thereby inhibiting the vomiting reflex and providing antiemetic activity. The metabolite's selectivity for 5-HT3 receptors makes it a valuable tool for studying serotonin's role in physiological processes.
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| ln Vitro |
In vitro studies have demonstrated that 7-Hydroxygranisetron hydrochloride is a biologically active molecule. It is classified among serotonin 5-HT3 receptor antagonists and exhibits cellular effects including anti-inflammatory and analgesic actions. Research has also investigated its capacity to inhibit cancer cell growth in controlled in vitro studies. As a major metabolite, its in vitro activity profile parallels that of the parent drug, Granisetron, which is a potent and selective 5-HT3 receptor antagonist. However, the specific IC50 values for the metabolite at the 5-HT3 receptor are less frequently reported than those for the parent compound.
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| ln Vivo |
In vivo, 7-Hydroxygranisetron contributes to the overall antiemetic effect observed after Granisetron administration. Following oral or intravenous dosing of Granisetron, the parent drug is extensively metabolized, primarily by hydroxylation, to form this 7-hydroxy metabolite. In animal models (rat, dog) and humans, this metabolite is the major circulating species. While the parent drug is highly potent, the metabolite is also pharmacologically active and can persist in the body, particularly after oral dosing. It is detectable in both plasma and urine, and its presence is used to confirm drug exposure in clinical trial subjects.
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| Enzyme Assay |
Non-cellular assays for 7-Hydroxygranisetron are typically radioligand binding assays used to assess 5-HT3 receptor affinity. A standard protocol involves using membranes prepared from cells expressing the human 5-HT3 receptor. These membranes are incubated with a fixed concentration of a high-affinity radioligand, such as [3H]GR65630 or [3H]BRL43694, in the presence of varying concentrations of the test compound (7-Hydroxygranisetron). Non-specific binding is determined using a high concentration of a known 5-HT3 antagonist (e.g., granisetron or ondansetron). After incubation and filtration, the bound radioactivity is counted. The IC50 is calculated from the displacement curve.
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| Cell Assay |
Cellular assays to assess the activity of 5-HT3 receptor antagonists often use cell lines that heterologously express the receptor, such as HEK-293 cells. A standard protocol involves loading these cells with a calcium-sensitive fluorescent dye (e.g., Fluo-4 AM). The cells are then stimulated with a 5-HT3 receptor agonist, such as 5-HT or 2-methyl-5-HT, which triggers an influx of calcium ions and a subsequent increase in fluorescence. 7-Hydroxygranisetron hydrochloride is added to the cells prior to agonist addition to measure its antagonist activity. A reduction in the fluorescence signal indicates successful blockade of the 5-HT3 receptor, and an IC50 can be calculated.
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| Animal Protocol |
The in vivo activity of Granisetron and its metabolites is often studied using a rodent model of emesis. Since rodents do not vomit, a surrogate model such as the "pica" model in rats is used, where kaolin (clay) consumption is measured as a behavioral indicator of nausea. A standard protocol involves injecting a chemotherapeutic agent (e.g., cisplatin) to induce nausea. Test compounds, including 7-Hydroxygranisetron, are administered intravenously or intraperitoneally prior to the emetic stimulus. The primary endpoint is the amount of kaolin consumed over 24 hours. A significant reduction in kaolin intake compared to the vehicle control indicates an anti-emetic effect, confirming the in vivo activity of the metabolite.
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| ADME/Pharmacokinetics |
The pharmacokinetics of 7-Hydroxygranisetron are well-documented as it is the major metabolite of the antiemetic drug Granisetron. In humans and animal models (dogs, rats), following administration of Granisetron, the metabolite is formed rapidly. The area under the plasma concentration-time curve (AUC) for the metabolite often exceeds that of the parent drug, particularly after oral administration. The time to reach peak concentration (Tmax) for the metabolite is typically delayed compared to the parent drug, reflecting the time required for metabolism. The metabolite and its conjugates are primarily excreted in the urine. The elimination half-life of the metabolite is generally similar to or longer than the parent compound.
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| Toxicity/Toxicokinetics |
The toxicity profile of 7-Hydroxygranisetron hydrochloride is expected to be similar to that of the parent drug, Granisetron, which is considered to have a favorable safety margin. Common side effects of Granisetron include headache, constipation, and asthenia (weakness). Serotonin syndrome is a rare but serious potential risk. As a reference standard, the pure metabolite is handled in a laboratory setting. Standard safety precautions include the use of personal protective equipment (lab coat, gloves, safety glasses) and working in a well-ventilated area. It is not intended for human consumption and is supplied for research use only, with purity typically exceeding 99% by HPLC.
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| Additional Infomation |
7-Hydroxygranisetron hydrochloride is a critical certified reference material in pharmaceutical analysis and clinical pharmacology. It is essential for the bioequivalence studies required for generic versions of Granisetron. Regulatory agencies mandate the quantification of both parent drug and major metabolites to demonstrate bioequivalence. This compound is used to ensure the accuracy and reproducibility of assays in toxicology and clinical trials. Its role is strictly analytical; it is not an active pharmaceutical ingredient for clinical use but rather a tool for drug development. The compound is stable and can be stored in powder form at -20degC for several years.
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| Molecular Formula |
C18H25CLN4O2
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|---|---|
| Molecular Weight |
364.87
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| CAS # |
133841-04-0
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| PubChem CID |
71749058
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| Appearance |
Solid powder
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| LogP |
3.339
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
25
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| Complexity |
474
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN1C2CCCC1CC(C2)NC(=O)C3=NN(C4=C3C=CC=C4O)C.Cl
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| Synonyms |
Metabolite D 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7407 mL | 13.7035 mL | 27.4070 mL | |
| 5 mM | 0.5481 mL | 2.7407 mL | 5.4814 mL | |
| 10 mM | 0.2741 mL | 1.3704 mL | 2.7407 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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