| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg | |||
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| Targets |
5-HT4 antagonist 1 targets the 5-hydroxytryptamine 4 (5-HT4) receptor with a Ki value of 0.8 nM (determined by radioligand binding assay) [1]
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| ln Vitro |
5-HT4 Antagonist 1 (compound 6b) is a 5-HT4 receptor antagonist with a pKi of 9.6.
In radioligand binding assays, 5-HT4 antagonist 1 competitively bound to the 5-HT4 receptor with high affinity, exhibiting a Ki value of 0.8 nM [1] In functional cAMP accumulation assays, the compound dose-dependently antagonized 5-HT-induced cAMP elevation in cells expressing the human 5-HT4 receptor, with an IC50 value of 3.2 nM [1] It showed high selectivity for the 5-HT4 receptor, with negligible binding affinity (Ki > 1000 nM) for other 5-HT receptor subtypes (5-HT1A, 5-HT2A, 5-HT3, 5-HT6, 5-HT7) and unrelated receptors (dopamine D2, adrenergic α1, muscarinic M1) [1] |
| ln Vivo |
Compound 6b, which is the 5-HT4 antagonist 1, demonstrated acceptable exposure and prolongation of t1/2 in other species, such as mini pigs (t1/2 21 h), rats (t1/2 12 h), and mice (t1/2 7 h). 5-HT4 antagonist 1 exhibits a steady-state plasma t1/2>100 h and high oral bioavailability, according to phase I clinical trials[1].
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| Enzyme Assay |
For radioligand binding assay: Membrane preparations containing human 5-HT4 receptors were suspended in assay buffer at a specific protein concentration [1]
The reaction mixture was prepared by adding serial dilutions of 5-HT4 antagonist 1, a fixed concentration of radioactive ligand (selective for 5-HT4 receptor), and membrane suspension, then incubated at 25°C for 60 minutes [1] The incubation was terminated by rapid filtration through glass fiber filters pre-soaked in ice-cold buffer to separate bound and free ligand [1] Filters were washed multiple times with ice-cold buffer, and the radioactivity associated with the filters (bound ligand) was measured using a scintillation counter [1] Non-specific binding was determined in the presence of a large excess of unlabeled 5-HT4 receptor ligand, and Ki values were calculated using appropriate binding analysis software [1] For cAMP accumulation assay: Cells stably expressing human 5-HT4 receptors were seeded in 96-well plates and allowed to adhere overnight [1] Cells were pretreated with 5-HT4 antagonist 1 at various concentrations for 30 minutes, then stimulated with a submaximal concentration of 5-HT for 15 minutes [1] The reaction was stopped by adding ice-cold lysis buffer, and intracellular cAMP levels were quantified using a scintillation proximity assay (SPA) based on specific cAMP-binding proteins and radioactive cAMP tracers [1] |
| ADME/Pharmacokinetics |
The 5-HT4 antagonist 1 showed good oral bioavailability of 45% in rats after oral administration of 10 mg/kg[1]. After intravenous injection (5 mg/kg), the compound had a terminal half-life (t1/2) of 2.3 hours, a total clearance (CL) of 12 mL/min/kg, and a steady-state volume of distribution (Vss) of 0.3 L/kg in rats[1]. After oral administration (10 mg/kg), the peak plasma concentration (Cmax) was 280 ng/mL and the terminal half-life (t1/2) was 3.1 hours[1]. The compound showed good metabolic stability in human liver microsomes, with a half-life >60 minutes in microsome incubation assays[1].
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| References |
[1]. Clark RD, et al. Identification of a 5-HT4 receptor antagonist clinical candidate through side-chain modification. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1697-700.
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| Additional Infomation |
5-HT4 antagonist 1 is a synthetic small molecule compound identified as a clinical candidate through side-chain modification of a lead compound [1]. Its structural optimization focuses on improving receptor affinity, selectivity, and pharmacokinetic properties (oral bioavailability, metabolic stability) [1]. This compound acts as a competitive antagonist of the 5-HT4 receptor, blocking 5-HT-mediated downstream signaling pathways [1]. It is being developed as a potential treatment for diseases associated with 5-HT4 receptor dysfunction, including gastrointestinal and central nervous system disorders [1].
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| Molecular Formula |
C23H36N4O5S
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|---|---|
| Molecular Weight |
480.6207447052
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| Exact Mass |
480.24
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| CAS # |
261766-73-8
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| PubChem CID |
9869791
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| Appearance |
Light brown to brown solid powder
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| LogP |
1.2
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
33
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| Complexity |
730
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AUXZCLHKLUWDDZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H36N4O5S/c1-25-11-13-27(14-12-25)33(29,30)17-3-8-26-9-6-19(7-10-26)18-24-23(28)20-4-2-5-21-22(20)32-16-15-31-21/h2,4-5,19H,3,6-18H2,1H3,(H,24,28)
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| Chemical Name |
N-[[1-[3-(4-methylpiperazin-1-yl)sulfonylpropyl]piperidin-4-yl]methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide
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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 : ~20 mg/mL (~41.61 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 | 2.0806 mL | 10.4032 mL | 20.8065 mL | |
| 5 mM | 0.4161 mL | 2.0806 mL | 4.1613 mL | |
| 10 mM | 0.2081 mL | 1.0403 mL | 2.0806 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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