ATOSIBAN ACETATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C43H67N11O12S2.C2H4O2
Molecular Weight	1054.241
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)=O.[H][C@]1(NC(=O)[C@@]([H])(NC(=O)[C@@H](CC2=CC=C(OCC)C=C2)NC(=O)CCSSC[C@H](NC(=O)[C@H](CC(N)=O)NC1=O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCN)C(=O)NCC(N)=O)[C@@H](C)CC)[C@@H](C)O

InChI

InChIKey=SVDWBHHCPXTODI-QIWYXCRTSA-N

InChI=1S/C43H67N11O12S2.C2H4O2/c1-5-23(3)35-41(63)53-36(24(4)55)42(64)50-29(20-32(45)56)38(60)51-30(43(65)54-17-8-10-31(54)40(62)49-27(9-7-16-44)37(59)47-21-33(46)57)22-68-67-18-15-34(58)48-28(39(61)52-35)19-25-11-13-26(14-12-25)66-6-2;1-2(3)4/h11-14,23-24,27-31,35-36,55H,5-10,15-22,44H2,1-4H3,(H2,45,56)(H2,46,57)(H,47,59)(H,48,58)(H,49,62)(H,50,64)(H,51,60)(H,52,61)(H,53,63);1H3,(H,3,4)/t23-,24+,27-,28+,29-,30-,31-,35-,36-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C43H67N11O12S2
Molecular Weight	994.189
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	9 / 9
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C2H4O2
Molecular Weight	60.052
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.medicines.org.uk/emc/medicine/4297

Atosiban (brand name Tractocile) is a competitive antagonist of human oxytocin at receptor level. In rats and guinea pigs, atosiban was shown to bind to oxytocin receptors, to decrease the frequency of contractions and the tone of the uterine musculature, resulting in a suppression of uterine contractions. Atosiban was also shown to bind to the vasopressin receptor, thus inhibiting the effect of vasopressin. Tractocile is indicated to delay imminent pre-term birth in pregnant adult women with: − regular uterine contractions of at least 30 seconds duration at a rate of ≥ 4 per 30 minutes − a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥ 50% − a gestational age from 24 until 33 completed weeks − a normal foetal heart rate. Atosiban does not have U.S. Food and Drug Administration (FDA) approval for use in the United States.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Oxytocin receptor 19 Target ID: CHEMBL2049 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16302826 \| https://www.ncbi.nlm.nih.gov/pubmed/7932368	Antagonist 2778		59.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Preterm birth 2 Sources: https://www.medicines.org.uk/emc/medicine/4297	Preventing		Approved 8429	Tractocile Approved Use Tractocile is indicated to delay imminent pre-term birth in pregnant adult women with: − regular uterine contractions of at least 30 seconds duration at a rate of ≥ 4 per 30 minutes − a cervical dilation of 1 to 3 cm (0-3 for nulliparas) and effacement of ≥ 50% − a gestational age from 24 until 33 completed weeks − a normal foetal heart rate Launch Date 2000

PubMed

Title	Date	PubMed
Receptor binding of oxytocin and vasopressin antagonists and inhibitory effects on isolated myometrium from preterm and term pregnant women.	1999 Oct	10519430
Atosiban for the primary prevention of preterm labour.	2001 Aug	11510718
The oxytocin antagonist atosiban versus the beta-agonist terbutaline in the treatment of preterm labor. A randomized, double-blind, controlled study.	2001 May	11328217
Gastric antisecretory and antiulcer activity of oxytocin in rats and guinea pigs.	2001 Nov 21	11764003
Design of oxytocin antagonists, which are more selective than atosiban.	2001 Sep	11587184
Development and clinical experience with the new evidence-based tocolytic atosiban.	2002 Jul	12190838
[Special management for threatened preterm delivery in multiple pregnancies].	2002 Nov	12454633
Pharmacological effects of oxytocin on gastric emptying and intestinal transit of a non-nutritive liquid meal in female rats.	2003 Apr	12690433
Effectiveness of nifedipine versus atosiban for tocolysis in preterm labour: a meta-analysis with an indirect comparison of randomised trials.	2003 Dec	14664874
Pharmacology of (2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino) -1-[(2'-methyl[1,1'-biphenyl]-4-yl)carbonyl]-2-pyrrolidinecarboxamide, a new potent and selective nonpeptide antagonist of the oxytocin receptor.	2003 Jul	12660315
Molecular modeling of the neurohypophyseal receptor/atosiban complexes.	2003 Jun	12871142
Female oxytocin-deficient mice display enhanced anxiety-related behavior.	2003 Jun	12746288
Emerging issues over the choice of nifedipine, beta-agonists and atosiban for tocolysis in spontaneous preterm labour--a proposed systematic review by the International Preterm Labour Council.	2004 Apr	15203610
The drugs we deserve.	2004 Apr	15008784
A prospective randomised trial of atosiban versus hexoprenaline for acute tocolysis and intrauterine resuscitation.	2004 Apr	15008765
Delaying preterm delivery at the threshold of viability.	2004 Jun	15203596
Sex differences and developmental effects of manipulations of oxytocin on alloparenting and anxiety in prairie voles.	2004 Mar	14994263
Oxytocin microinjected into dorsal motor nucleus of the vagus excites gallbladder motility via NMDA receptor-NO-cGMP pathway.	2005 Jan 25	15680949
Tocolytic therapy and clinical experience. Combination therapy.	2005 Mar	15715603
Binding domains of the oxytocin receptor for the selective oxytocin receptor antagonist barusiban in comparison to the agonists oxytocin and carbetocin.	2005 Mar 7	15740719

Patents

Sample Use Guides

In Vivo Use Guide

Tractocile (Atosiban) is administered intravenously in three successive stages: an initial bolus dose (6.75 mg), performed with Tractocile 6.75 mg/0.9 ml solution for injection, immediately followed by a continuous high dose infusion (loading infusion 300 micrograms/min) of Tractocile 37.5 mg/5 ml concentrate for solution for infusion during three hours, followed by a lower dose of Tractocile 37.5 mg/5 ml concentrate for solution for infusion (subsequent infusion 100 micrograms/min) up to 45 hours. The duration of the treatment should not exceed 48 hours. The total dose given during a full course of Tractocile therapy should preferably not exceed 330.75 mg of atosiban. Intravenous therapy using the initial bolus injection should be started as soon as possible after diagnosis of pre-term labour. Once the bolus has been injected, proceed with the infusion (See Summary of Product Characteristics of Tractocile 37.5 mg/5 ml, concentrate for solution for infusion). In the case of persistence of uterine contractions during treatment with Tractocile, alternative therapy should be considered.

Route of Administration: Intravenous

In Vitro Use Guide

Atosiban had significant inhibitory effects on myometrial contractions of myometrial strips from healthy pregnant women at concentrations as low as 1 ug/mL.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:44:58 GMT 2023` Edited by `admin` on `Fri Dec 15 15:44:58 GMT 2023`
Record UNII	0P5DNO7CEF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ATOSIBAN ACETATE

Common Name

English

ATOSIBAN ACETATE [EMA EPAR]

Common Name

English

OXYTOCIN, 1-(3-MERCAPTOPROPANOIC ACID)-2-(O-ETHYL-D-TYROSINE)-4-L-THREONINE-8-L-ORNITHINE-, ACETATE

Common Name

English

GLYCINAMIDE, O-ETHYL-N-(3-MERCAPTO-1-OXOPROPYL)-D-TYROSYL-L-ISOLEUCYL-L-THREONYL-L-ASPARAGINYL-L-CYSTEINYL-L-PROLYL-L-ORNITHYL-, CYCLIC (1->5)-DISULFIDE, MONOACETATE (SALT)

Common Name

English

GLYCINAMIDE, O-ETHYL-N-(3-MERCAPTO-1-OXOPROPYL)-D-TYROSYL-L-ISOLEUCYL-L-THREONYL-L-ASPARAGINYL-L-CYSTEINYL-L-PROLYL-L-ORNITHYL-, CYCLIC (1->5)-DISULPHIDE, MONOACETATE (SALT)

Common Name

English

GLYCINAMIDE, O-ETHYL-N-(3-MERCAPTO-1-OXOPROPYL)-D-TYROSYL-L-ISOLEUCYL-L-THREONYL-L-ASPARAGINYL-L-CYSTEINYL-L-PROLYL-L-ORNITHYL-, CYCLIC (1->5)-DISULPHIDE, ACETATE (1:1)

Common Name

English

Atosiban acetate [WHO-DD]

Common Name

English

GLYCINAMIDE, O-ETHYL-N-(3-MERCAPTO-1-OXOPROPYL)-D-TYROSYL-L-ISOLEUCYL-L-THREONYL-L-ASPARAGINYL-L-CYSTEINYL-L-PROLYL-L-ORNITHYL-, CYCLIC (1->5)-DISULFIDE, ACETATE (1:1)

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98292