| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
Velusetrag targets the serotonin 5-HT4 receptor (5-HT4R), a G protein-coupled receptor that modulates gastrointestinal motility, neurotransmitter release, and cognition. By stimulating 5-HT4 receptors, it enhances acetylcholine release and promotes coordinated peristalsis. It shows >500-fold selectivity over other 5-HT receptors.
|
|---|---|
| ln Vitro |
HEK-293 cells transfected with the h5-HT4(c) receptor exhibit a concentration-dependent rise in cAMP in response to velusetrag (10 pM-100 μM), with a pEC50 of 8.3 [1]. The guinea pig colonic longitudinal muscle/myenteric plexus (LMMP) contracts in response to velusetrag (100 pM-1 μM) in a concentration-dependent manner, with a pEC50 of 7.9 [1]. With a pEC50 of 7.9, TD-5108 (0.001-10 μM) causes concentration-dependent relaxation of the precontracted rat esophagus in response to carbachol (3 μM) [1].
In vitro, Velusetrag is a potent and selective 5-HT4 receptor agonist with a pKi of 7.7. It exhibits no affinity for 5-HT2A and 5-HT2B receptors (Ki >10 μM). In HEK-293 cells stably expressing 5-HT4 receptors, it stimulates cAMP accumulation. |
| ln Vivo |
In PD mice, a single intraperitoneal injection of velusetrag (3 mg/kg) greatly enhances the facilitation of contextual fear extinction [3]. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibit an increase in cAMP levels in the hippocampus when administered with velusetrag (3 mg/kg) intraperitoneally [3]. In guinea pigs, velusetrag (0.003-3 mg/kg; single subcutaneous injection) shortens the time needed for dye excretion and accelerates intestinal transit in a dose-dependent manner [2]. In line with esophageal relaxation in rats, velusetrag (0.003–1 mg/kg; single intravenous administration) dose-dependently increases intercrystalline distance [2].
In vivo, Velusetrag is used to investigate gastrointestinal motility and serotonergic regulation of gut function. By stimulating 5-HT4 receptors, it enhances acetylcholine release and promotes coordinated peristalsis, making it valuable in studies of gastroparesis, constipation, and functional GI disorders. |
| Enzyme Assay |
In vitro receptor binding assays for Velusetrag are performed using membrane preparations expressing human 5-HT4 receptors. Radioligand competition binding assays are used to measure the compound's affinity for 5-HT4R, and the pKi (7.7) is calculated from competition curves. Selectivity is assessed by testing the compound against a panel of other serotonin receptors.
|
| Cell Assay |
In vitro cellular assays for Velusetrag are performed using HEK-293 cells stably expressing 5-HT4 receptors. Cells are treated with the compound, and cAMP accumulation is measured using ELISA or HTRF assays. The EC50 for stimulation of cAMP production is calculated from concentration-response curves.
|
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (7-8 weeks old) were injected with MPTP[3].
Doses: 3 mg/kg. Route of Administration: single ip. Experimental Results: Improved facilitation of contextual fear extinction. There was no improvement in impaired rotarod performance in PD mice. In vivo animal experiments for Velusetrag are conducted in rodent models of gastrointestinal motility disorders. A typical protocol involves oral administration of the compound, followed by assessment of gastric emptying, intestinal transit, and colonic motility. Efficacy is evaluated by measuring the acceleration of gastrointestinal transit and improvement in motility parameters. |
| ADME/Pharmacokinetics |
Velusetrag hydrochloride has a molecular weight of 541.10. It is an orally active compound. Further PK details, including half-life, bioavailability, and tissue distribution, are available from the manufacturer's data sheets.
|
| Toxicity/Toxicokinetics |
Toxicological data for Velusetrag hydrochloride are not extensively reported. As a research-use compound, its safety profile has not been formally evaluated in comprehensive preclinical toxicology studies. The compound is intended for research purposes only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
|
| References |
|
| Additional Infomation |
Velusetrag hydrochloride is also known as TD-5108 hydrochloride. It is an orally active, potent, and selective agonist of the serotonin 5-HT4 receptor with a pKi of 7.7. It is used to investigate gastrointestinal motility and serotonergic regulation of gut function. This product is for research use only.
|
| Molecular Formula |
C25H37CLN4O5S
|
|---|---|
| Molecular Weight |
541.104
|
| Exact Mass |
540.217
|
| CAS # |
866933-51-9
|
| Related CAS # |
Velusetrag;866933-46-2
|
| PubChem CID |
11842632
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
36
|
| Complexity |
932
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
Cl.S(C)(N(C)C[C@@H](CN1[C@H]2CC(C[C@@H]1CC2)NC(C1=CC2C=CC=CC=2N(C(C)C)C1=O)=O)O)(=O)=O
|
| InChi Key |
BLIKSWRONBYRDD-BCDHGJHMSA-N
|
| InChi Code |
InChI=1S/C25H36N4O5S.ClH/c1-16(2)29-23-8-6-5-7-17(23)11-22(25(29)32)24(31)26-18-12-19-9-10-20(13-18)28(19)15-21(30)14-27(3)35(4,33)34;/h5-8,11,16,18-21,30H,9-10,12-15H2,1-4H3,(H,26,31);1H/t18?,19-,20+,21-;/m0./s1
|
| Chemical Name |
N-[(1S,5R)-8-[(2R)-2-hydroxy-3-[methyl(methylsulfonyl)amino]propyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-oxo-1-propan-2-ylquinoline-3-carboxamide;hydrochloride
|
| Synonyms |
TD 5108; TD-5108; Velusetrag hydrochloride
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO : ~220 mg/mL (~406.58 mM)
H2O : ~10 mg/mL (~18.48 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.5 mg/mL (10.16 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 55.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5.5 mg/mL (10.16 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 55.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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: ≥ 5.5 mg/mL (10.16 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 | 1.8481 mL | 9.2404 mL | 18.4809 mL | |
| 5 mM | 0.3696 mL | 1.8481 mL | 3.6962 mL | |
| 10 mM | 0.1848 mL | 0.9240 mL | 1.8481 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
