Cebranopadol

Summary

Cebranopadol (CHEMBL2364605) is a phase-3 clinical-stage small molecule targeting OPRD1, OPRK1, and OPRM1; indicated across 5 conditions including osteoarthritis, knee and diabetic neuropathy.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 4 (OPRD1, OPRK1, OPRM1…)
• Indications: 5 conditions
• Clinical trials: 14
• Chemistry: 378.5 Da · C24H27FN2O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2364605
Name	Cebranopadol
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11848225
Molecular formula	C24H27FN2O
Molecular weight	378.5
InChIKey	CSMVOZKEWSOFER-UHFFFAOYSA-N

SMILES: CN(C)C1(CCC2(CC1)C3=C(CCO2)C4=C(N3)C=CC(=C4)F)C5=CC=CC=C5

IUPAC name: 6-fluoro-N,N-dimethyl-1’-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4’-cyclohexane]-1’-amine

Also known as: Cebranopadol, GRT-6005, GRT6005, CEBRANOPADOL

Parent form; salt/anhydrous children: CHEMBL3325957

Patent coverage: 93 distinct patent families (252 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 168 (67%) of the total. 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
OPRD1	δ receptor	Agonist	7.74	0.2%	P41143
OPRK1	κ receptor	Agonist	8.59	0%	P41145
OPRM1	μ receptor	Agonist	9.15	0%	P35372
OPRL1	NOP receptor	Agonist	7.89	0.3%	P41146

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: Nociceptin receptor, Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 9 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OPRM1	9.49	EC50	0.32	nM	CHEMBL_ACT_25868682
OPRM1	9.15	Ki	0.7	nM	CHEMBL_ACT_19426881
OPRL1	9.05	Ki	0.9	nM	CHEMBL_ACT_19426880
OPRM1	8.92	EC50	1.2	nM	CHEMBL_ACT_19426883
OPRD1	8.42	IC50	3.77	nM	CHEMBL_ACT_25868805
OPRM1	7.95	EC50	11.28	nM	CHEMBL_ACT_25868738
OPRL1	7.89	EC50	13	nM	CHEMBL_ACT_19426882
OPRL1	7.34	EC50	45.46	nM	CHEMBL_ACT_25868846
OPRK1	6.78	EC50	166	nM	CHEMBL_ACT_25868820

Target pathways

Aggregated over 4 target gene(s): OPRD1, OPRK1, OPRM1, OPRL1.

Top Reactome pathways

6 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	4	OPRD1, OPRK1, OPRL1, OPRM1
G alpha (i) signalling events	4	OPRD1, OPRK1, OPRL1, OPRM1
Interleukin-4 and Interleukin-13 signaling	2	OPRD1, OPRM1
MECP2 regulates neuronal receptors and channels	2	OPRK1, OPRM1
Opioid Signalling	1	OPRM1
G-protein activation	1	OPRM1

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	4
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	4
phospholipase C-activating G protein-coupled receptor signaling pathway	4
neuropeptide signaling pathway	4
G protein-coupled opioid receptor signaling pathway	4
signal transduction	4
sensory perception	3
sensory perception of pain	3
immune response	2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
response to nicotine	2
eating behavior	2
response to ethanol	2
adult locomotory behavior	1
negative regulation of gene expression	1

Indications & clinical

Indications

5 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
osteoarthritis, knee	2	MONDO:0005416	EFO:0004616
diabetic neuropathy	2	MONDO:0006626	MONDO:0001583
drug dependence	1	MONDO:0005303	EFO:0003890

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 14.

Phase distribution

Phase	Trials
PHASE2	6
PHASE3	4
PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01964378	PHASE3	TERMINATED	CORAL - Cebranopadol Versus Morphine Prolonged-release in Patients With Chronic Moderate to Severe Pain Related to Cancer
NCT02031432	PHASE3	COMPLETED	CORAL XT - Open-label Extension Trial of the CORAL Trial
NCT06423703	PHASE3	COMPLETED	A Study of Cebranopadol for the Treatment of Acute Pain After Bunionectomy
NCT06545097	PHASE3	COMPLETED	A Study of Cebranopadol for the Treatment of Acute Pain After Abdominoplasty
NCT00872885	PHASE2	COMPLETED	Bunionectomy Trial With GRT6005
NCT00878293	PHASE2	COMPLETED	Painful Diabetic Polyneuropathy Trial With a New Centrally Acting Analgesic
NCT01347671	PHASE2	COMPLETED	Safety and Efficacy of GRT6005 in Pain Due to Diabetic Polyneuropathy
NCT01357837	PHASE2	COMPLETED	Assessment of GRT6005 in Painful Osteoarthritis of the Knee
NCT01709214	PHASE2	COMPLETED	Safety and Efficacy Study of GRT6005 in Patients With Osteoarthritis (OA) Knee Pain
NCT01939366	PHASE2	COMPLETED	Cebranopadol Efficacy and Safety in Diabetic Patients Suffering From Chronic Pain Caused by Damage to the Nerves
NCT03757559	PHASE1	COMPLETED	A Trial to Evaluate the Abuse Potential of 3 Doses of GRT6005 in Adult Non-dependent Recreational Opioid Users
NCT03882762	PHASE1	COMPLETED	A Clinical Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics of Cebranopadol
NCT05256108	PHASE1	COMPLETED	Assessment of Abuse Potential of Cebranopadol in Humans
NCT05491785	PHASE1	COMPLETED	Cebranopadol Effects on Ventilatory Drive, Central Nervous System (CNS) and Pain.

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.

612 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
BUPRENORPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRL1, OPRM1
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRL1, OPRM1
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TAFAMIDIS	ChEMBL + PubChem	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ALVIMOPAN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMIODARONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMLODIPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
AMOXAPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BENZTROPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
BUTORPHANOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CANNABIDIOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CINNARIZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
CODEINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ECONAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FENTANYL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
HYDROCODONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
HYDROMORPHONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LANSOPRAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LEVORPHANOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LOPERAMIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
LOXAPINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MEPERIDINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
METHADONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
METHYLNALTREXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MICONAZOLE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
MORPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALBUPHINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALFURAFINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALMEFENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALOXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NALTREXONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
NELFINAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OLICERIDINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OXYCODONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
OXYMORPHONE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PAROXETINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PASIREOTIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PENTAZOCINE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
PIMOZIDE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
RALOXIFENE	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
RITONAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SAMIDORPHAN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SAQUINAVIR	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
SUNITINIB	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TAMOXIFEN	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
TRAMADOL	ChEMBL	Phase 4 (approved)	OPRD1, OPRK1, OPRM1
ASIMADOLINE	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
ATICAPRANT	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
NAVACAPRANT	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
TRIMEBUTINE	ChEMBL	Phase 3	OPRD1, OPRK1, OPRM1
BREMAZOCINE	ChEMBL	Phase 2	OPRD1, OPRK1, OPRM1
CARFENTANIL	ChEMBL	Phase 2	OPRD1, OPRK1, OPRM1