Retosiban

Summary

Retosiban (CHEMBL429736) is a phase-3 clinical-stage small molecule targeting OXTR; indicated across 1 condition.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (OXTR)
• Indications: 1 condition
• Clinical trials: 8
• Chemistry: 494.6 Da · C27H34N4O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL429736
Name	Retosiban
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11340891
Molecular formula	C27H34N4O5
Molecular weight	494.6
InChIKey	PLVGDGRBPMVYPB-FDUHJNRSSA-N

SMILES: CC[C@H](C)[C@@H]1C(=O)N[C@@H](C(=O)N1[C@H](C2=COC(=N2)C)C(=O)N3CCOCC3)C4CC5=CC=CC=C5C4

IUPAC 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

Also known as: GSK-221149, GSK-221149A, GSK221149, GSK221149A, Retosiban, RETOSIBAN

Patent coverage: 28 distinct patent families (99 SureChEMBL compound mentions), from 2 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
OXTR	OT receptor	Antagonist	9.19	0.1%	P30559

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Vasopressin V2 receptor, Oxytocin receptor.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 5 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OXTR	9.2	Ki	0.63	nM	CHEMBL_ACT_3465719
OXTR	9.19	Ki	0.65	nM	CHEMBL_ACT_2089512
OXTR	9	Ki	1	nM	CHEMBL_ACT_2089467
OXTR	8.39	Ki	4.1	nM	CHEMBL_ACT_2089513
AVPR2	6.02	Ki	950	nM	CHEMBL_ACT_2089516

Target pathways

Aggregated over 1 target gene(s): OXTR.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Vasopressin-like receptors	1	OXTR
G alpha (q) signalling events	1	OXTR

Dominant GO biological processes

GO term	Targets
regulation of systemic arterial blood pressure by vasopressin	1
muscle contraction	1
cell surface receptor signaling pathway	1
G protein-coupled receptor signaling pathway	1
female pregnancy	1
lactation	1
cellular response to hormone stimulus	1
positive regulation of blood pressure	1
positive regulation of vasoconstriction	1
maternal process involved in parturition	1
positive regulation of cold-induced thermogenesis	1
system process	1
signal transduction	1
regulation of biological quality	1

Indications & clinical

Indications

1 indication record carries no mapped disease name (EFO/MeSH-only); none shown.

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE1	5
PHASE3	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02292771	PHASE3	TERMINATED	A Randomized Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban for Women in Spontaneous Preterm Labour
NCT02292784	PHASE3	COMPLETED	Follow up Study to Assess Long Term Safety and Outcomes in Infants and Children Born to Mothers Participating in Retosiban Treatment Studies
NCT00404768	PHASE2	COMPLETED	The Safety, Tolerability And Metabolism Of GSK221149A, In Pregnant Women (30-36 Weeks), In Pre-Term Labor
NCT00449709	PHASE1	TERMINATED	A Study To Assess The Pharmacokinetics Of Different Modified Release Formulations Of GSK221149 In Healthy Adult Subjects
NCT00457925	PHASE1	COMPLETED	Absorption, Distribution, Metabolism And Excretion Study For GSK221149A
NCT01627587	PHASE1	COMPLETED	A Two Cohort Study to Look at the Metabolites of GSK221149, the Metabolism of GSK221149 Administered With a High Fat Meal and With Ketoconazole
NCT01702376	PHASE1	COMPLETED	This Study Will Investigate the Effect of Single Oral Doses of Retosiban on Cardiac Repolarization, With Moxifloxacin as a Positive Control in Healthy Volunteers.
NCT01867996	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Retosiban (GSK221149) When Dosed With Efavirenz (EFZ)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

15 molecules share ≥1 primary target. Top 15 by shared-target count:

Molecule	Source	Status	Shared targets
OXYTOCIN	ChEMBL + PubChem	Phase 4 (approved)	OXTR
ATOSIBAN	ChEMBL	Phase 4 (approved)	OXTR
CARBETOCIN	ChEMBL	Phase 4 (approved)	OXTR
DESMOPRESSIN	ChEMBL	Phase 4 (approved)	OXTR
MOZAVAPTAN	ChEMBL	Phase 4 (approved)	OXTR
VASOPRESSIN	ChEMBL	Phase 4 (approved)	OXTR
LIXIVAPTAN	ChEMBL	Phase 3	OXTR
NOLASIBAN	ChEMBL	Phase 3	OXTR
SEMAXANIB	ChEMBL	Phase 3	OXTR
EPELSIBAN	ChEMBL	Phase 2	OXTR
NELIVAPTAN	ChEMBL	Phase 2	OXTR
ORNIPRESSIN	ChEMBL	Phase 2	OXTR
PECAVAPTAN	ChEMBL	Phase 2	OXTR
SELEPRESSIN	ChEMBL	Phase 2	OXTR
Belzutifan	PubChem	Approved	OXTR