ATOSIBAN ACETATE

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C43H67N11O12S2.C2H4O2
Molecular Weight	1054.2445
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

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 2849		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 8583	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
Atosiban for the primary prevention of preterm labour.	2001 Aug	11510718
Effects of oxytocin receptor antagonist atosiban on pregnant myometrium in vitro.	2001 Jul	11430968
Oxytocin antagonist disrupts hypotension-evoked renin secretion and other responses in conscious rats.	2001 Mar	11171655
Oxytocin decreases carrageenan induced inflammation in rats.	2001 Sep	11514032
Involvement of oxytocin and vasopressin in the pathophysiology of preterm labor and primary dysmenorrhea.	2002	12436949
Effects of mating stimuli and oxytocin on plasma cortisol concentration in gilts.	2002 Mar	14666160
Oxytocin antagonists for tocolysis in preterm labour -- a systematic review.	2002 Nov	12444392
Exploring the role of Tractocile in everyday clinical practice.	2003 Apr	12763126
The development and introduction of anti-oxytocic tocolytics.	2003 Apr	12763125
Preterm labour: an overview of current and emerging therapeutics.	2003 Aug	12871140
Preterm delivery: an overview.	2003 Aug	12848639
Evidence that oxytocin is a physiological component of LH regulation in non-pregnant women.	2003 Jul	12832367
The oxytocin receptor.	2003 Jul	12826328
Molecular modeling of the neurohypophyseal receptor/atosiban complexes.	2003 Jun	12871142
Oxytocin and fetal membranes in preterm labor: current concepts and clinical implication.	2003 Jun	12857435
The effects of a progesterone metabolite, 5 beta-dihydroprogesterone, on oxytocin receptor binding in human myometrial membranes.	2003 Jun	12798477
Endogenous oxytocin excites phasic contraction of gallbladder in rabbits through oxytocin receptor.	2003 Sep 30	14672277
Spinal effects of oxytocin on uterine motility in anesthetized rats.	2004 Aug	15044182
Current medical therapy in the prevention and treatment of preterm labour.	2004 Dec	15691786
Tocolysis and preterm labour.	2004 Dec	15534440
Preterm birth.	2004 Jun	15652088
Delaying preterm delivery at the threshold of viability.	2004 Jun	15203596
The oxytocin receptor antagonist atosiban inhibits cell growth via a "biased agonist" mechanism.	2005 Apr 22	15705593
Inhibition of trigemino-hypoglossal reflex in rats by oxytocin is mediated by mu and kappa opioid receptors.	2005 Feb 21	15713278
Tocolytic therapy and clinical experience. Combination therapy.	2005 Mar	15715603
Design of peptide oxytocin antagonists with strikingly higher affinities and selectivities for the human oxytocin receptor than atosiban.	2005 Oct	15880385

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.

Name

Type

Language

ATOSIBAN ACETATE [EMA EPAR]

Preferred Name

English

ATOSIBAN ACETATE

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