| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| Other Sizes |
| Targets |
(S)-Setastine is a selective and potent antagonist of the histamine H1 receptor, a GPCR. By binding to the H1 receptor on various cells (e.g., endothelial cells, smooth muscle cells), it prevents the binding and downstream effects of histamine, a key mediator of allergic responses. This antagonism blocks the signaling pathways that lead to vasodilation (causing redness), increased vascular permeability (causing edema), and stimulation of sensory nerves (causing itching). Its non-sedating property is due to its poor penetration of the blood-brain barrier.
|
|---|---|
| ln Vitro |
In vitro, (S)-Setastine potently inhibits H1 receptor-mediated responses. Its affinity for the H1 receptor is typically measured by radioligand binding displacement assays using [3H]pyrilamine or [3H]mepyramine on human recombinant H1 receptors expressed in CHO cells. The compound has a high binding affinity (Ki typically <10 nM). As an antagonist, it prevents histamine-induced calcium mobilization and smooth muscle contraction. It shows no significant activity at other receptors (e.g., muscarinic, adrenergic, or serotonergic) at pharmacologically relevant concentrations.
|
| ln Vivo |
In vivo, (S)-Setastine has been shown to have a long-lasting antihistamine effect and good oral efficacy. It is effective in animal models of allergic conditions, such as histamine-induced paw edema in rats and passive cutaneous anaphylaxis (PCA) in mice. Oral administration (e.g., 1-10 mg/kg) significantly inhibits histamine-induced skin reactions. Its long duration of action (up to 24 hours) and lack of central nervous system (CNS) side effects (sedation, cognitive impairment) make it a desirable antihistamine. It can be used in the research of allergic diseases.
|
| Enzyme Assay |
Non-cellular assays for (S)-Setastine are radioligand binding assays. Membranes from CHO cells stably expressing the human H1 receptor (5-10 ug protein) are incubated with 1 nM [3H]pyrilamine (or [3H]mepyramine) in 50 mM Tris-HCl buffer (pH 7.4). (S)-Setastine is added at varying concentrations (0.1-1000 nM). Non-specific binding is determined in the presence of 10 uM diphenhydramine. After a 60-minute incubation at 25degC, the reaction is terminated by filtration through GF/B filters, and the retained radioactivity is counted. The Ki is calculated from the displacement curve using the Cheng-Prusoff equation. This assay determines the binding affinity of the compound for the H1 receptor.
|
| Cell Assay |
Cellular assays are performed using CHO cells expressing the human H1 receptor and a Ca2+-sensitive fluorescent dye (e.g., Fluo-4 AM). Cells are seeded in 96-well plates. After loading with the dye, cells are treated with (S)-Setastine (0.1-1000 nM) for 10 minutes and then stimulated with a EC₈0 concentration of histamine (e.g., 100 nM). The increase in intracellular calcium is measured as a fluorescence increase. (S)-Setastine causes a rightward shift in the histamine dose-response curve, confirming its competitive antagonism. The pA2 or IC₅0 is calculated. This functional assay confirms the antagonist activity.
|
| Animal Protocol |
A rat model of histamine-induced paw edema is a standard in vivo test for antihistamine efficacy. Male Wistar rats are fasted overnight. (S)-Setastine (0.1, 0.3, 1, 3 mg/kg) or vehicle is administered orally. One hour later, 50 uL of 1% histamine solution is injected into the right hind paw. Paw volume is measured using a plethysmometer at 0, 30, 60, and 120 minutes post-injection. The percentage inhibition of edema is calculated. Cetirizine (1 mg/kg) is used as a positive control. (S)-Setastine potently inhibits histamine-induced paw swelling with an ED₅0 of approximately 0.3-0.5 mg/kg, demonstrating its in vivo antihistamine efficacy.
|
| ADME/Pharmacokinetics |
(S)-Setastine has a molecular weight of 357.92 g/mol and a predicted logP of approximately 5.5. It is a white to off-white solid powder. It is soluble in DMSO and ethanol. In vivo, it is well absorbed after oral administration, with good oral efficacy. Its duration of action is long (up to 24 hours) due to its high receptor affinity and favorable pharmacokinetics. It is metabolized in the liver (likely by CYP3A4) and excreted in urine and bile. The compound should be stored as a powder at -20degC, protected from light. In solution, store at -80degC for up to 6 months.
|
| Toxicity/Toxicokinetics |
(S)-Setastine has a favorable safety profile as an H1 antagonist. Its lack of CNS penetration makes it non-sedating. Potential side effects at high doses may include mild anticholinergic effects (dry mouth). Standard safety precautions for handling research chemicals (gloves, lab coat, goggles) should be used. The compound is for research use only and is not an FDA-approved drug.
|
| References | |
| Additional Infomation |
(S)-Setastine ((S)-EGIS-2062 free acid, CAS 2241669-86-1) is a non-sedating, highly potent antihistamine. It represents a pure enantiomer approach for improved pharmacological specificity. Setastine itself has been used in some countries as an antihistamine, but this (S)-enantiomer is primarily a research tool for studying H1 receptor pharmacology and for developing improved antihistamines with reduced side effects. It is for research use only.
|
| Molecular Formula |
C22H28CLNO
|
|---|---|
| Molecular Weight |
357.92
|
| Appearance |
White to off-white solid powder
|
| Synonyms |
(S)-EGIS-2062 free acid; (S)-EGYT-2062 free acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~279.39 mM; with ultrasonication)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (13.97 mM) (saturation unknown) in 10% DMSO +40% PEG300 +5% Tween-80 +45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution。
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (13.97 mM) (saturation unknown) in 10% DMSO +90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution。 For example, if 1 mL of working solution is to be prepared, You can add 100 μL of the 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix well. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (13.97 mM) (saturation unknown) in 10% DMSO +90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution。 |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7939 mL | 13.9696 mL | 27.9392 mL | |
| 5 mM | 0.5588 mL | 2.7939 mL | 5.5878 mL | |
| 10 mM | 0.2794 mL | 1.3970 mL | 2.7939 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
