Repositioning Candidate Details
| Candidate ID: | R1206 |
| Source ID: | DB09059 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Atosiban |
| Synonyms: | Atosiban |
| Molecular Formula: | C43H67N11O12S2 |
| SMILES: | [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)N1CCC[C@H]1C(=O)N[C@@H](CCCN)C(=O)NCC(N)=O)[C@@H](C)CC)[C@@H](C)O |
| Structure: |
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| DrugBank Description: | Atosiban is an inhibitor of the hormones oxytocin and vasopressin. It is used intravenously to halt premature labor. Although initial studies suggested it could be used as a nasal spray and hence would not require hospital admission, it is not used in that form. Atobisan was developed by the Swedish company Ferring Pharmaceuticals. It was first reported in the literature in 1985. Atosiban is licensed in proprietary and generic forms for the delay of imminent pre-term birth in pregnant adult women. |
| CAS Number: | 90779-69-4 |
| Molecular Weight: | 994.19 |
| DrugBank Indication: | Atosiban is indicated for use in delaying imminent pre-term birth in pregnant adult women with: - regular uterine contractions of at least 30 s duration at a rate of at least 4 per 30 min - a cervical dilation of 1-3cm (0-3cm for nulliparas) and effacement of at least 50% - a gestational age of 24-33 weeks - a normal fetal heart rate |
| DrugBank Pharmacology: | Atosiban reduces the frequency of uterine contractions to delay pre-term birth in adult females and induces uterine quiescence . |
| DrugBank MoA: | Atosiban is a synthetic peptide oxytocin antagonist . It resembles oxytocin with has modifications at the 1, 2, 4, and 8 positions. The N-terminus of the cysteine residue is deaminated to form 3-mercaptopropanic acid at position 1, at position 2 L-tyrosine is modified to D-tyrosine with an ethoxy group replacing the phenol , threonine replaces glutamine at postion 4, and ornithine replaces leucine at position 8. It binds to membrane bound oxytocin receptors on the myometrium and prevents oxytocin-stimulated increases in inositol triphosphate production . This ultimately prevents release of stored calcium from the sarcoplasmic reticulum and subsequent opening of voltage gated calcium channels. This shutdown of cytosolic calcium increase prevents contractions of the uterine muscle, reducing the frequency of contractions and inducing uterine quiescence. Atosiban has more recently been found to act as a biased ligand at oxytocin receptors . It acts as an antagonist of Gq coupling, explaining the inhibition of the inositol triphosphate pathway thought to be responsible for the effect on uterine contraction, but acts as an agonist of Gi coupling. This agonism produces a pro-inflammatory effect in the human amnion, activating pro-inflammatory signal tranducer NF-κB . It is thought that this reduces atosiban's effectiveness compared to agents which do not produce inflammation as inflammatory mediators are known to play a role in the induction of labour. |
| Targets: | Oxytocin receptor antagonist; Vasopressin V1a receptor antagonist; Vasopressin V1b receptor antagonist; Vasopressin V2 receptor antagonist |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
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