Retosiban (GSK-221149; GSK-221149A) is a novel, potent, orally bioactive, and selective, sub-nanomolar oxytocin receptor antagonist with Ki of 0.65 nM and >1400-fold selectivity over the related vasopressin receptors. The procontractile effect of stretch on the human myometrium is inhibited by retisiban. Retosiban inhibited the stimulation of human myometrial contractility induced by stretch. One possible method for preventing preterm birth in multiple pregnancies is the use of retisiban treatment. GlaxoSmithKline is developing the medication Retosiban to treat premature labor. It has been demonstrated that in the anesthetized rat, GSK221149A inhibits oxytocin-induced uterine contractions.

Physicochemical Properties

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
CAS #	820957-38-8
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
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
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Oxytocin ( IC50 = 0.65 nM )
References	[1]. The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4.
Additional Infomation	Retosiban is a dipeptide. Retosiban has been used in trials studying the treatment of Premature Labor and Obstetric Labour, Premature. Drug Indication Treatment of spontaneous preterm labour

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~202.2 mM )

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. 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. 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 corn oil and mix evenly.  (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.