| Identification | More | [Name]
Atosiban | [CAS]
90779-69-4 | [Synonyms]
ATOSIBAN ACETATE
1-deamino-2d-tyr-(oet)-4-thr-8-orn-oxytocin
oxytocin,1-(3-mercaptopropanoicacid)-2-(o-ethyl-d-tyrosine)-4-l-threonine-8-l
rwj22164
1-(3-Mercaptopropionic acid)-2-(3-(p-ethoxyphenyl)-D-alanine)-4-L-thre onine-8-L-ornithineoxytocin
[Mpr-D-Tyr(OEt)-Ile-Thr-Asn-Cys]-Pro-Orn-Gly-NH2
(2S)-N-[(1S)-4-Amino-1-(carbamoylmethylcarbamoyl)butyl]-1-[(4S,7S,13S,16R)-13-[(2S)-butan-2-yl]-7-(carbamoylmethyl)-16-[(4-ethoxyphenyl)methyl]-10-(1-hydroxyethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]pyrrolidine-2-carboxamide
1-(3-Mercaptopropanoic acid)-2-(O-ethyl-D-tyrosine)-4-L-threonine-8-L-ornithineoxytocin
1-Deamino-2-D-Tyr-(O-ethyl)-4-Thr-8-ornoxytocin
Atosiban
Human Atosiban
1-Deamino-2-D-Tyr-(O-ethyl)-4-Thr-8-ornoxytocin, Tractocile, 1-(3-Mercaptopropanoic acid)-2-(O-ethyl-D-tyrosine)-4-L-threonine-8-L-ornithineoxytocin | [EINECS(EC#)]
806-815-5 | [Molecular Formula]
C45H71N11O14S2 | [MDL Number]
MFCD00672436 | [Molecular Weight]
994.19 | [MOL File]
90779-69-4.mol |
| Chemical Properties | Back Directory | [Melting point ]
>165oC (dec.) | [Boiling point ]
1469.0±65.0 °C(Predicted) | [density ]
1.254±0.06 g/cm3(Predicted) | [storage temp. ]
−20°C
| [solubility ]
H2O: ≤100 mg/mL
| [form ]
solid
| [pka]
12.81±0.70(Predicted) | [color ]
White to Off-White | [Water Solubility ]
Soluble to 50 mg/ml in water | [CAS DataBase Reference]
90779-69-4(CAS DataBase Reference) |
| Hazard Information | Back Directory | [Description]
Atosiban was introduced in the UK as an injectable inhibitor of preterm labor, a major
cause of infant morbidity and mortality. This peptidic oxytocin analog is an antagonist of
the vasopressin V1a receptor and of the oxytocin receptor which is found in dramatically
increased concentration in the uterine myometrium of pregnant women near term. It
competitively inhibited contractions in the pregnant guinea pig uterus induced by oxytocin
and vasopressin. In a multicenter, double-blind, placebo-controlled trial, treatment with
atosiban caused pregnancy prolongation for up to 7 days in women with more than 28
weeks of gestation. In a comparative clinical trial, atosiban showed a comparable tocolytic
action (uterine relaxant) to ritodrine but the former was significantly better tolerated,
especially with regards to maternal cardiovascular side effects. In healthy volunteers,
plasma levels of atosiban decreased bi-exponentially with an initial and a terminal half-life of 21 min and 1.7h respectively. | [Originator]
Ferring AB (Sweden) | [Uses]
Atosiban is an oxytocin receptor blocking agent in the treatment of experimental endometriosis and was shown exhibit significant therapeutic efficiency. | [Uses]
Premature labor | [Definition]
ChEBI: Atosiban is an oligopeptide. | [Indications]
Atosiban is an analogue of oxytocin that is modified at
positions 1, 2, 4, and 8. It is a competitive inhibitor of
oxytocin binding. Early studies have demonstrated that
this drug does decrease and stop uterine contractions.
Atosiban is not available for use in the United States. | [Manufacturing Process]
BocGly resin (3.0 g, 3 meq) was placed in the reaction vessel of a Vega Model
50 semiautomatic peptide synthesizer. The peptide was built up by increments
on the resin in accordance with Tables 1 and 2.
Activation of the amino acid was carried out by dissolving 10 meq of a
suitably protected amino acid, 15 meq of hydroxy benzotriazole and 10 meq
of dicyclohexylcarbodiimide in DMF (70 ml), whereupon the mixture was left
at room temperature for 1 h (asparagine and glutamine were activated at 0°C
for 15 min), whereupon the precipitate was filtered off, and the filtrate was
treated the activated amino acid in Table 1 (step 7). The completion of the
coupling step was checked by the method of Kaiser (Anal. Biochem. 34, 595
(1970)) after the cycle had been completed (step 9). If the test was positive
(coupling yield below 99%), the cycle was repeated starting from step 7. If
the test was negative, the termination procedure was performed according to
Table 2. When the whole sequence had been coupled, the resin was placed on
a filter and washed repeatedly with methanol. The dried product was placed in
a glass vessel and cooled in an ethanol-dry ice bath and suspended in
methanol (about 100 ml). The mixture was then saturated with sodium-dried
ammonia to achieve approximately 50% concentration. Then the vessel was
placed in a steel cylinder and left at room temperature for two days. After the
pressure had been relieved, the product was filtered, and the residue was
extracted with hot (about 100°C) DMF (2x100 ml). The filtrate and the extract
were combined and evaporated. The residue was dissolved in a small amount
of hot DMF, and methanol was added to the coupling point. The precipitate
was collected by filtration and washed on the filter with methanol. After drying
in vacuum, the purity was checked by thin-layer chromatography. Yield about
2.8 g.
100 mg of the above described protected peptide were placed in a 100 ml round-bottom flask, and dry nitrogen was flushed through for about 15 min.
50 ml of sodium-dried ammonia were distilled in, and the protective group
was removed from the product by adding sodium until blue color remained in
the solution for 15 sec. The excess of sodium was destroyed by adding of
ammonium chloride. Ammonia was removed in a nitrogen stream, and the
residue was dissolved in 1 liter of methanol. The pH of the solution was
adjusted to about 4 with concentrated acetic acid, and the solution was then
titrated with 0.1 mM of iodine in methanol to brownish color. The mixture was
stirred with 3 g of Dowex 50x2 ion exchanger in chloride form for 10 min at
room temperature. The ion exchanger was removed by filtration, and the
filtrate was evaporated to dryness. The residue was dissolved in 3 ml of 20%
acetic acid and purified by chromatography on Sephadex G-25 with 20%
acetic acid as eluent. The final purification was achieved by reverse phase
HPLC. The purity of the product was determined on a HPCL column μ-
Bondapak C-18 in 45% ethanol and 55% 5 mM trifluoroacetic acid in water.
The column was supplied by Water Associates, Inc., Millford, Mass., U.S.A. The
purity of the product was also shown by amino acid analysis. | [Brand name]
Tractocile, Antocin | [Therapeutic Function]
Oxytocin antagonist | [Biochem/physiol Actions]
Atosiban efficiently prevent preterm uterine contractions without any major cardiovascular, pulmonary or central nervous system side effects. It has potential to treat preterm labour. | [Anticancer Research]
The antitumor effects of the essential oil of O. falcata were tested in transplantedmurine H22 solid tumors in vivo. Growth inhibition in H22 solid tumors was moderate(Yang et al. 2013). | [storage]
Store at -20°C |
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