| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Retosiban (GSK221149) targets the Oxytocin Receptor (OTR), a class A G protein-coupled receptor (GPCR). The oxytocin receptor is primarily responsible for mediating uterine contractions during labor. In vivo, oxytocin binding to its receptor in the myometrium triggers Gq/11 signaling, leading to increased intracellular calcium (Ca2+) and subsequent contraction of uterine smooth muscle. Antagonists of this receptor are developed as tocolytics (drugs to prevent preterm labor).
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| ln Vitro |
Retosiban (GSK221149A) is a potent and selective oxytocin antagonist with a Ki of 0.65 nM and exhibits >1400-fold selectivity over the related vasopressin receptors (V1a, V1b, V2). The (S)-isomer is the inactive isomer. In vitro, the active Retosiban potently inhibits oxytocin-induced calcium mobilization and inositol phosphate accumulation in cells expressing the human oxytocin receptor. The (S)-isomer shows negligible antagonist activity at the receptor.
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| ln Vivo |
The active compound Retosiban has demonstrated in vivo efficacy. It is an orally bioactive and selective oxytocin receptor antagonist. In animal models of preterm labor (e.g., late-term pregnant rats), oral administration of active Retosiban effectively suppresses uterine contractions and delays parturition. The (S)-Retosiban isomer is used as a negative control in these in vivo experiments to ensure that the tocolytic effects observed are mediated specifically by oxytocin receptor antagonism.
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| Enzyme Assay |
The binding affinity of the parent active compound Retosiban is determined using a radioligand binding assay. Membranes from CHO cells expressing the human oxytocin receptor are incubated with [125I]-d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT (a radiolabeled oxytocin antagonist) in the presence of varying concentrations of test compound. After incubation, the mixture is filtered, and bound radioactivity is counted. The Ki is calculated using the Cheng-Prusoff equation. For the (S)-isomer, the Ki is >1000 nM (inactive).
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| Cell Assay |
An intracellular calcium mobilization assay is used to assess antagonist function. HEK-293 cells expressing the human oxytocin receptor are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4). Cells are pre-incubated with the test compound, then stimulated with a submaximal concentration of oxytocin. The reduction in fluorescence signal compared to oxytocin alone indicates antagonist activity. The (S)-isomer shows no inhibition of the oxytocin-induced calcium signal.
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| Animal Protocol |
The isomer is not used for in vivo treatment. For the active Retosiban, in vivo efficacy is typically tested in the rat model of preterm labor. Timed-pregnant rats (day 21 of gestation, term is 22-23 days) are dosed orally with the test compound (e.g., 3-30 mg/kg). Uterine contractions are measured via intrauterine pressure catheters. The latency to delivery and number of pups delivered are recorded. The (S)-isomer is used as a control compound in these studies.
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| ADME/Pharmacokinetics |
(S)-Retosiban has a molecular weight of 494.58. As an inactive isomer, its PK profile is not usually studied in depth. The active Retosiban is an orally bioavailable small molecule. It is characterized as having high permeability and moderate half-life suitable for oral dosing to treat acute conditions like preterm labor. The compound is stored as a powder at -20degC and is soluble in DMSO and other organic solvents for formulation.
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| Toxicity/Toxicokinetics |
The inactive isomer is non-toxic at control concentrations. The active Retosiban has a favorable safety profile in preclinical species, with no significant off-target effects given its high selectivity (>1400-fold vs. vasopressin receptors). Because oxytocin is also involved in social bonding and postpartum physiology, chronic antagonism could theoretically have effects on these processes, but these are not relevant to its acute tocolytic application in research settings.
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| References | |
| Additional Infomation |
Retosiban (GSK221149A) is a potent and selective oxytocin antagonist developed by GlaxoSmithKline for the treatment of preterm labor. The active compound has progressed to clinical trials for the management of spontaneous preterm labor. The (S)-isomer is an important reference standard for analytical method development and a negative control for biological assays. This product is for research use only (RUO).
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| Molecular Formula |
C27H34N4O5
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| Molecular Weight |
494.58
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| CAS # |
2994298-20-1
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| Related CAS # |
Retosiban;820957-38-8
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| Appearance |
White to off-white solid powder
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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 :~200 mg/mL (~404.38 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (10.11 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 50.0 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 mg/mL (10.11 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 50.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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.
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