| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Oxytocin ( IC50 = 0.65 nM )
Retosiban targets the oxytocin receptor, a G protein-coupled receptor that mediates the effects of oxytocin. It acts as a potent and selective antagonist with no detectable agonist activity. Retosiban has nanomolar affinity for the oxytocin receptor with >1400-fold selectivity over the closely related vasopressin receptors. By blocking the oxytocin receptor, it inhibits uterine contractions. |
|---|---|
| ln Vitro |
In vitro, Retosiban (0.1-10 μM) causes a parallel rightward shift of the oxytocin-induced concentration-response curve in rat isolated myometrial strips. Retosiban (1 μM) attenuates the effect of stretch on myometrial contractility under high tension. It has nanomolar affinity for the oxytocin receptor with no detectable agonist activity.
|
| ln Vivo |
Retosiban inhibits spontaneous and induced uterine contractions. It is a potent, selective, and orally active oxytocin receptor antagonist that can be studied in research for preterm labor. The compound's oral bioavailability supports its use in preclinical models of preterm labor. Specific animal model data are detailed in the referenced studies.
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| Enzyme Assay |
The oxytocin receptor binding assay for Retosiban involves incubating the compound with membrane preparations from cells expressing the human or rat oxytocin receptor and a radiolabeled oxytocin ligand. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. The Ki for displacement of the radioligand is calculated from the competition curve.
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| Cell Assay |
To evaluate the cellular activity of Retosiban, cells expressing the oxytocin receptor are seeded in 96-well plates and loaded with a calcium-sensitive fluorescent dye. Cells are pre-incubated with varying concentrations of Retosiban and then stimulated with oxytocin. The intracellular calcium flux is measured using a fluorescence plate reader. The IC50 for inhibition of oxytocin-induced calcium flux is calculated.
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| Animal Protocol |
The in vivo efficacy of Retosiban is evaluated in animal models of preterm labor, such as pregnant rat models. Animals are treated with Retosiban orally at various doses, and uterine contractions are measured using an intrauterine pressure catheter. The compound's ability to inhibit uterine contractions and delay preterm delivery is assessed.
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| ADME/Pharmacokinetics |
Retosiban is characterized as being orally active. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 494.58 and a molecular formula of C27H34N4O5. It is soluble in DMSO and is typically stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Retosiban are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent and selective oxytocin receptor antagonist, and its safety profile has been evaluated in preclinical studies. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
Retosiban is a dipeptide. Retosiban has been used in clinical trials to investigate the treatment of preterm birth and obstetric preterm birth.
Drug Indications Treatment of spontaneous preterm birth Retosiban (GSK221149A) is a potent, selective, and orally active oxytocin receptor antagonist with a Ki of 0.65 nM for the human oxytocin receptor and a Ki of 4.1 nM for the rat oxytocin receptor. It has >1400-fold selectivity over vasopressin receptors. It inhibits spontaneous and induced uterine contractions and can be studied in research for preterm labor. |
| Molecular Formula |
C27H34N4O5
|
|---|---|
| Molecular Weight |
494.58266
|
| Exact Mass |
494.253
|
| Elemental Analysis |
C, 65.57; H, 6.93; N, 11.33; O, 16.17
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| CAS # |
820957-38-8
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| Related CAS # |
(S)-Retosiban
|
| PubChem CID |
11340891
|
| Appearance |
Off-white to yellow solid powder
|
| LogP |
2.191
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
36
|
| Complexity |
819
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
[C@H](C1=COC(C)=N1)(N1C(=O)[C@@H](C2CC3C=CC=CC=3C2)NC(=O)[C@H]1[C@@H](C)CC)C(N1CCOCC1)=O
|
| InChi Key |
PLVGDGRBPMVYPB-FDUHJNRSSA-N
|
| InChi Code |
InChI=1S/C27H34N4O5/c1-4-16(2)23-25(32)29-22(20-13-18-7-5-6-8-19(18)14-20)26(33)31(23)24(21-15-36-17(3)28-21)27(34)30-9-11-35-12-10-30/h5-8,15-16,20,22-24H,4,9-14H2,1-3H3,(H,29,32)/t16-,22+,23+,24+/m0/s1
|
| Chemical Name |
(3R,6R)-6-[(2S)-butan-2-yl]-3-(2,3-dihydro-1H-inden-2-yl)-1-[(1R)-1-(2-methyl-1,3-oxazol-4-yl)-2-morpholin-4-yl-2-oxoethyl]piperazine-2,5-dione
|
| Synonyms |
GSK221,149; GSK 221,149; GSK-221,149; GSK221149; GSK 221149; GSK-221149; Retosiban; GSK221149A; GSK 221149A; GSK-221149A
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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)
|
| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~202.2 mM )
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.05 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 25.0 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: ≥ 2.5 mg/mL (5.05 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 25.0 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: ≥ 2.5 mg/mL (5.05 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 | 2.0219 mL | 10.1096 mL | 20.2192 mL | |
| 5 mM | 0.4044 mL | 2.0219 mL | 4.0438 mL | |
| 10 mM | 0.2022 mL | 1.0110 mL | 2.0219 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01867996 | Completed | Drug: Retosiban Drug: EFZ 600 mg |
Obstetric Labour, Premature | GlaxoSmithKline | June 11, 2013 | Phase 1 |
| NCT02377414 | Completed | Drug: Placebo Drug: Retosiban solution for Infusion |
Obstetric Labour, Premature | GlaxoSmithKline | March 2, 2015 | Phase 1 |
| NCT01702376 | Completed | Drug: Retosiban 100 mg Drug: Retosiban 800 mg Drug: Placebo |
Obstetric Labour, Premature | GlaxoSmithKline | October 3, 2012 | Phase 1 |
| NCT02292784 | Completed | Drug: Retosiban Drug: Atosiban Drug: Placebo |
Obstetric Labour, Premature | GlaxoSmithKline | June 1, 2015 | Phase 3 |
| NCT00404768 | Completed | Drug: GSK221149A Drug: Placebo |
Obstetric Labour, Premature | GlaxoSmithKline | October 12, 2007 | Phase 2 |
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