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Naldemedine

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Also known as NaldemedinaS-297995NA

Summary

Naldemedine (CHEMBL2105755) is an approved small molecule (ATC A06AH05) targeting OPRD1 and OPRM1; indicated across 2 conditions including constipation disorder and pancreatitis.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: A06AH05
  • Targets: 2 (OPRD1, OPRM1)
  • Indications: 2 conditions
  • Clinical trials: 11
  • Chemistry: 570.6 Da · C32H34N4O6

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL2105755
NameNaldemedine
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID54732242
ATCA06AH05
Molecular formulaC32H34N4O6
Molecular weight570.6
InChIKeyAXQACEQYCPKDMV-RZAWKFBISA-N

SMILES: CC(C)(C1=NC(=NO1)C2=CC=CC=C2)NC(=O)C3=C([C@H]4[C@@]56CCN([C@@H]([C@@]5(C3)O)CC7=C6C(=C(C=C7)O)O4)CC8CC8)O

IUPAC name: (4R,4aS,7aR,12bS)-3-(cyclopropylmethyl)-4a,7,9-trihydroxy-N-[2-(3-phenyl-1,2,4-oxadiazol-5-yl)propan-2-yl]-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-6-carboxamide

Also known as: Naldemedina, Naldemedine, S-297995, NALDEMEDINE, NA

Parent form; salt/anhydrous children: CHEMBL3039508

Patent coverage: 98 distinct patent families (269 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 237 (88%) 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).

GeneTargetActionpAffinityCancer dependencyUniProt
OPRD1δ receptorAntagonist9.040.2%P41143
OPRM1μ receptorAntagonist8.950%P35372

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Mu-type opioid receptor, Delta-type opioid receptor.

Bioactivity

ChEMBL activities: 4 potent at pChembl ≥ 5 of 4 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
OPRD19.04Ki0.91nMCHEMBL_ACT_18874895
OPRM18.96Ki1.1nMCHEMBL_ACT_18874874
OPRM18.5IC503.16nMCHEMBL_ACT_29322748
OPRM15.46IC503500nMCHEMBL_ACT_29322764

Target pathways

Aggregated over 2 target gene(s): OPRD1, OPRM1.

Top Reactome pathways

6 total, by targets touching each:

PathwayTargetsGenes
Peptide ligand-binding receptors2OPRD1, OPRM1
G alpha (i) signalling events2OPRD1, OPRM1
Interleukin-4 and Interleukin-13 signaling2OPRD1, OPRM1
Opioid Signalling1OPRM1
G-protein activation1OPRM1
MECP2 regulates neuronal receptors and channels1OPRM1

Dominant GO biological processes

GO termTargets
G protein-coupled receptor signaling pathway2
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger2
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway2
phospholipase C-activating G protein-coupled receptor signaling pathway2
neuropeptide signaling pathway2
G protein-coupled opioid receptor signaling pathway2
signal transduction2
immune response1
adult locomotory behavior1
negative regulation of gene expression1
negative regulation of protein-containing complex assembly1
response to nicotine1
eating behavior1
response to ethanol1
regulation of mitochondrial membrane potential1

Indications & clinical

Indications

1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

IndicationPhaseMONDOEFO
constipation disorder4MONDO:0002203HP:0002019

1 disease in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)PhaseMONDOEFO
pancreatitis2MONDO:0004982EFO:0000278

Clinical trials

Total trials: 11.

Phase distribution

PhaseTrials
PHASE24
PHASE33
Not specified2
PHASE41
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07038551PHASE4COMPLETEDProphylactic Use of Naldemedine on Opioid-induced Nausea and Vomiting in Patients With Cancer: POSEIDON Study
NCT01965158PHASE3COMPLETEDEfficacy and Safety of Naldemedine in the Treatment of Opioid-induced Constipation
NCT01965652PHASE3COMPLETEDLong Term Safety of Naldemedine
NCT01993940PHASE3COMPLETEDEfficacy and Safety of Naldemedine in Treating Opioid-induced Constipation
NCT05588323PHASE1/PHASE2RECRUITINGSafety and Pharmacokinetics Study of Naldemedine in Paediatric Participants Receiving Opioids
NCT01122030PHASE2COMPLETEDStudy to Evaluate the Safety and Efficacy of Naldemedine (S-297995) for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain
NCT01443403PHASE2COMPLETEDA Study of Naldemedine (S-297995) for the Treatment of Opioid-Induced Constipation in Adults With Non-Malignant Chronic Pain Receiving Opioid Therapy
NCT04355169PHASE2TERMINATEDA Study of Naldemedine in Participants Undergoing Surgeries That Include a Bowel Resection or Bowel Transection
NCT06334198PHASE2UNKNOWNThe Effect of Naldemedine on Opioid-induced Bowel Dysfunction
NCT03720613Not specifiedRECRUITINGRisk of Major Adverse Cardiovascular Events for Naldemedine & Other Medications for Opioid Induced Constipation
NCT07231796Not specifiedRECRUITINGNaldemedine in Clinical Practice in Cancer Patients With Opioid Induced CONstipation: Clinical Outcomes and Patient Experience

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

448 molecules share ≥1 primary target. Top 100 by shared-target count:

MoleculeSourceStatusShared targets
DihydroergotamineChEMBL + PubChemPhase 4 (approved)OPRD1, OPRM1
EluxadolineChEMBL + PubChemPhase 4 (approved)OPRD1, OPRM1
PROPOXYPHENEChEMBL + PubChemPhase 4 (approved)OPRD1, OPRM1
REGORAFENIBChEMBL + PubChemPhase 4 (approved)OPRD1, OPRM1
TAFAMIDISChEMBL + PubChemPhase 4 (approved)OPRD1, OPRM1
ALFENTANILChEMBLPhase 4 (approved)OPRD1, OPRM1
ALVIMOPANChEMBLPhase 4 (approved)OPRD1, OPRM1
AMIODARONEChEMBLPhase 4 (approved)OPRD1, OPRM1
AMLODIPINEChEMBLPhase 4 (approved)OPRD1, OPRM1
AMOXAPINEChEMBLPhase 4 (approved)OPRD1, OPRM1
ASTEMIZOLEChEMBLPhase 4 (approved)OPRD1, OPRM1
BAZEDOXIFENEChEMBLPhase 4 (approved)OPRD1, OPRM1
BENZTROPINEChEMBLPhase 4 (approved)OPRD1, OPRM1
BUPRENORPHINEChEMBLPhase 4 (approved)OPRD1, OPRM1
BUTORPHANOLChEMBLPhase 4 (approved)OPRD1, OPRM1
CANDESARTAN CILEXETILChEMBLPhase 4 (approved)OPRD1, OPRM1
CANNABIDIOLChEMBLPhase 4 (approved)OPRD1, OPRM1
CHLORPROMAZINEChEMBLPhase 4 (approved)OPRD1, OPRM1
CINNARIZINEChEMBLPhase 4 (approved)OPRD1, OPRM1
CLOTRIMAZOLEChEMBLPhase 4 (approved)OPRD1, OPRM1
CODEINEChEMBLPhase 4 (approved)OPRD1, OPRM1
DAUNORUBICINChEMBLPhase 4 (approved)OPRD1, OPRM1
DIETHYLSTILBESTROLChEMBLPhase 4 (approved)OPRD1, OPRM1
ECONAZOLEChEMBLPhase 4 (approved)OPRD1, OPRM1
FENTANYLChEMBLPhase 4 (approved)OPRD1, OPRM1
FLUPHENAZINEChEMBLPhase 4 (approved)OPRD1, OPRM1
FLUSPIRILENEChEMBLPhase 4 (approved)OPRD1, OPRM1
HYDROCODONEChEMBLPhase 4 (approved)OPRD1, OPRM1
HYDROMORPHONEChEMBLPhase 4 (approved)OPRD1, OPRM1
LANSOPRAZOLEChEMBLPhase 4 (approved)OPRD1, OPRM1
LEVORPHANOLChEMBLPhase 4 (approved)OPRD1, OPRM1
LOPERAMIDEChEMBLPhase 4 (approved)OPRD1, OPRM1
LOXAPINEChEMBLPhase 4 (approved)OPRD1, OPRM1
MEPERIDINEChEMBLPhase 4 (approved)OPRD1, OPRM1
METHADONEChEMBLPhase 4 (approved)OPRD1, OPRM1
METHYLNALTREXONEChEMBLPhase 4 (approved)OPRD1, OPRM1
METHYLNALTREXONE BROMIDEChEMBLPhase 4 (approved)OPRD1, OPRM1
MICONAZOLEChEMBLPhase 4 (approved)OPRD1, OPRM1
MONTELUKASTChEMBLPhase 4 (approved)OPRD1, OPRM1
MORPHINEChEMBLPhase 4 (approved)OPRD1, OPRM1
NAFTOPIDILChEMBLPhase 4 (approved)OPRD1, OPRM1
NALBUPHINEChEMBLPhase 4 (approved)OPRD1, OPRM1
NALFURAFINEChEMBLPhase 4 (approved)OPRD1, OPRM1
NALMEFENEChEMBLPhase 4 (approved)OPRD1, OPRM1
NALOXEGOLChEMBLPhase 4 (approved)OPRD1, OPRM1
NALOXONEChEMBLPhase 4 (approved)OPRD1, OPRM1
NALTREXONEChEMBLPhase 4 (approved)OPRD1, OPRM1
NELFINAVIRChEMBLPhase 4 (approved)OPRD1, OPRM1
OLICERIDINEChEMBLPhase 4 (approved)OPRD1, OPRM1
OXICONAZOLEChEMBLPhase 4 (approved)OPRD1, OPRM1
OXYCODONEChEMBLPhase 4 (approved)OPRD1, OPRM1
OXYMORPHONEChEMBLPhase 4 (approved)OPRD1, OPRM1
PACLITAXELChEMBLPhase 4 (approved)OPRD1, OPRM1
PALBOCICLIBChEMBLPhase 4 (approved)OPRD1, OPRM1
PAROXETINEChEMBLPhase 4 (approved)OPRD1, OPRM1
PASIREOTIDEChEMBLPhase 4 (approved)OPRD1, OPRM1
PENTAZOCINEChEMBLPhase 4 (approved)OPRD1, OPRM1
PERHEXILINEChEMBLPhase 4 (approved)OPRD1, OPRM1
PHENOXYBENZAMINEChEMBLPhase 4 (approved)OPRD1, OPRM1
PIMOZIDEChEMBLPhase 4 (approved)OPRD1, OPRM1
RALOXIFENEChEMBLPhase 4 (approved)OPRD1, OPRM1
RIFAMPINChEMBLPhase 4 (approved)OPRD1, OPRM1
RIFAXIMINChEMBLPhase 4 (approved)OPRD1, OPRM1
RITONAVIRChEMBLPhase 4 (approved)OPRD1, OPRM1
ROTIGOTINEChEMBLPhase 4 (approved)OPRD1, OPRM1
SAMIDORPHANChEMBLPhase 4 (approved)OPRD1, OPRM1
SAQUINAVIRChEMBLPhase 4 (approved)OPRD1, OPRM1
SUNITINIBChEMBLPhase 4 (approved)OPRD1, OPRM1
TAMOXIFENChEMBLPhase 4 (approved)OPRD1, OPRM1
TELMISARTANChEMBLPhase 4 (approved)OPRD1, OPRM1
TRAMADOLChEMBLPhase 4 (approved)OPRD1, OPRM1
ZIMELDINEChEMBLPhase 4 (approved)OPRD1, OPRM1
ASIMADOLINEChEMBLPhase 3OPRD1, OPRM1
ATICAPRANTChEMBLPhase 3OPRD1, OPRM1
CEBRANOPADOLChEMBLPhase 3OPRD1, OPRM1
NAVACAPRANTChEMBLPhase 3OPRD1, OPRM1
TIANEPTINEChEMBLPhase 3OPRD1, OPRM1
TRIMEBUTINEChEMBLPhase 3OPRD1, OPRM1
AXELOPRANChEMBLPhase 2OPRD1, OPRM1
AZD-7268ChEMBLPhase 2OPRD1, OPRM1
BREMAZOCINEChEMBLPhase 2OPRD1, OPRM1
CARFENTANILChEMBLPhase 2OPRD1, OPRM1
CLINAFLOXACINChEMBLPhase 2OPRD1, OPRM1
CLOTHIAPINEChEMBLPhase 2OPRD1, OPRM1
CP-866087ChEMBLPhase 2OPRD1, OPRM1
CYCLAZOCINEChEMBLPhase 2OPRD1, OPRM1
DIPRENORPHINEChEMBLPhase 2OPRD1, OPRM1
ETORPHINEChEMBLPhase 2OPRD1, OPRM1
FLUNARIZINEChEMBLPhase 2OPRD1, OPRM1
METAZOCINEChEMBLPhase 2OPRD1, OPRM1
NALORPHINEChEMBLPhase 2OPRD1, OPRM1
NIGULDIPINEChEMBLPhase 2OPRD1, OPRM1
ORGANONChEMBLPhase 2OPRD1, OPRM1
PENFLURIDOLChEMBLPhase 2OPRD1, OPRM1
SPIRADOLINEChEMBLPhase 2OPRD1, OPRM1
THIOPROPERAZINEChEMBLPhase 2OPRD1, OPRM1
AfatinibPubChemApprovedOPRD1, OPRM1
ApixabanPubChemApprovedOPRD1, OPRM1
BinimetinibPubChemApprovedOPRD1, OPRM1
BosentanPubChemApprovedOPRD1, OPRM1

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot