| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Pumosetrag HCl targets the 5-HT3 receptor, a ligand-gated ion channel that is a member of the serotonin receptor family. It acts as a partial agonist at the 5-HT3 receptor, meaning it produces a submaximal response even at full receptor occupancy. By modulating 5-HT3 receptor activity in the gastrointestinal tract, pumosetrag influences intestinal motility, secretion, and visceral sensitivity. The compound promotes fasting preduodenal migrating motor complex activity, delays liquid stomach emptying, is linked to proximal gastric relaxation, and quickens intestinal transit.
|
|---|---|
| ln Vitro |
In vitro, pumosetrag acts on 5-HT3 receptors in the gastrointestinal tract. It promotes fasting preduodenal migrating motor complex activity and modulates intestinal motility. In tissue response studies, ondansetron (a 5-HT3 antagonist) inhibits the tissue response to pumosetrag, confirming its action on 5-HT3 receptors. The compound's partial agonist activity at 5-HT3 receptors allows it to modulate receptor activity without producing the full effects of a full agonist.
|
| ln Vivo |
Pumosetrag demonstrates species and region specificity. Pumosetrag exhibited comparable efficacy and potency to 5-HT in the rat proximal colon, but was less effective than 5-HT in the ileum, jejunum, and distal colon of rats. In the guinea pig intestine, pompetrag exhibits a distinct activity profile and outperforms 5-HT across the board. In the mouse gut, Pumosetrag elicited minimal reaction. In rats and guinea pigs, ondansetron inhibits the tissue response to Pumosetrag, confirming its action on 5-HT(3) receptors [1]. Pumosetrag promotes fasting preduodenal migrating motor complex activity, delays liquid stomach emptying, is linked to proximal gastric relaxation, and quickens intestinal transit [2].
In vivo, pumosetrag accelerates gastrointestinal transit, increases stool frequency, and improves straining and the sensation of incomplete evacuation in patients with IBS-C. It promotes fasting preduodenal migrating motor complex activity, delays liquid stomach emptying, is linked to proximal gastric relaxation, and quickens intestinal transit. The compound has been proposed as a treatment for IBS-C. Its effects on gastrointestinal motility make it a potential therapeutic for functional gastrointestinal disorders. |
| Enzyme Assay |
Non-cellular in vitro assays for pumosetrag involve receptor binding studies. A standard protocol uses membrane preparations from cells expressing recombinant human 5-HT3 receptors. The membranes are incubated with a radiolabeled ligand, such as [³H]GR65630, and varying concentrations of pumosetrag. Non-specific binding is determined in the presence of an excess of unlabeled ondansetron. After incubation, the reaction is terminated by rapid filtration, and the radioactivity bound to the membranes is measured. The Ki or IC50 values are calculated from the competition curves.
|
| Cell Assay |
Cellular assays for pumosetrag are performed using cell lines expressing 5-HT3 receptors, such as HEK293 cells stably transfected with the receptor. Cells are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4) and then stimulated with varying concentrations of pumosetrag or a 5-HT3 agonist such as serotonin. The increase in intracellular calcium concentration is measured using a fluorescence plate reader. The EC50 for receptor activation is determined from the concentration-response curve. The partial agonist activity is confirmed by comparing the maximal response to that of a full agonist.
|
| Animal Protocol |
In vivo animal studies for pumosetrag are conducted in rodent models of gastrointestinal motility. Rats or guinea pigs are administered pumosetrag orally or intraperitoneally. Gastrointestinal transit is assessed by measuring the distance traveled by a fluorescent or charcoal marker after a specified time. Gastric emptying is measured by assessing the retention of a test meal. Intestinal motility can be assessed by recording intraluminal pressure. The compound's effects on these parameters are compared to vehicle controls and to reference compounds such as ondansetron.
|
| ADME/Pharmacokinetics |
Pumosetrag HCl has a molecular weight not specified in the available literature. It is an orally available small molecule. For in vivo studies, it can be formulated in standard vehicles for oral administration. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have not been fully reported in the available literature. However, its oral activity and efficacy in preclinical models suggest it is absorbed and reaches sufficient concentrations to exert its pharmacological effects.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for pumosetrag have not been extensively reported. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed when handling pumosetrag, including the use of personal protective equipment. No specific toxicity data, such as LD50 values, are available in the provided literature.
|
| References | |
| Additional Infomation |
Pumosetrag HCl (MKC-733; DDP-733) is an orally available, small-molecule 5-HT3 receptor partial agonist. It has been proposed for patients with irritable bowel syndrome with constipation (IBS-C). Pumosetrag accelerates gastrointestinal transit, increases stool frequency, and improves straining and the sensation of incomplete evacuation. The compound promotes fasting preduodenal migrating motor complex activity, delays liquid stomach emptying, and quickens intestinal transit. Pumosetrag is not a clinically approved drug and has not entered recent clinical trials. Its primary application is in research on gastrointestinal motility and functional bowel disorders.
|
| Molecular Formula |
C15H18CLN3O2S
|
|---|---|
| Molecular Weight |
339.83
|
| Exact Mass |
339.08
|
| CAS # |
194093-42-0
|
| Related CAS # |
153062-94-3 (Pumosetrag free base);
|
| PubChem CID |
154103
|
| Appearance |
White to off-white solid powder
|
| Boiling Point |
529.9ºC at 760mmHg
|
| Flash Point |
274.3ºC
|
| Vapour Pressure |
2.59E-11mmHg at 25°C
|
| LogP |
2.728
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
22
|
| Complexity |
499
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1CN2CCC1[C@H](C2)NC(=O)C3=CNC4=C(C3=O)SC=C4.Cl
|
| InChi Key |
XGVADZZDFADEOO-YDALLXLXSA-N
|
| InChi Code |
InChI=1S/C15H17N3O2S.ClH/c19-13-10(7-16-11-3-6-21-14(11)13)15(20)17-12-8-18-4-1-9(12)2-5-18;/h3,6-7,9,12H,1-2,4-5,8H2,(H,16,19)(H,17,20);1H/t12-;/m0./s1
|
| Chemical Name |
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-oxo-4H-thieno[3,2-b]pyridine-6-carboxamide;hydrochloride
|
| Synonyms |
DDP733DDP-733 MKC-733 DDP 733 MKC 733MKC733
|
| 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 : ~12 mg/mL (~35.31 mM)
H2O : ~2.94 mg/mL (~8.65 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.2 mg/mL (3.53 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 12.0 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: 1.2 mg/mL (3.53 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.0 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: ≥ 1.2 mg/mL (3.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 4.55 mg/mL (13.39 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9426 mL | 14.7132 mL | 29.4265 mL | |
| 5 mM | 0.5885 mL | 2.9426 mL | 5.8853 mL | |
| 10 mM | 0.2943 mL | 1.4713 mL | 2.9426 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
