Nalfurafine

Summary

Nalfurafine (CHEMBL267495) is an approved small molecule (ATC V03AX02) targeting OPRK1.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: V03AX02
• Targets: 1 (OPRK1)
• Clinical trials: 6
• Chemistry: 476.6 Da · C28H32N2O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL267495
Name	Nalfurafine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	6445230
ATC	V03AX02
Molecular formula	C28H32N2O5
Molecular weight	476.6
InChIKey	XGZZHZMWIXFATA-UEZBDDGYSA-N

SMILES: CN([C@@H]1CC[C@]2([C@H]3CC4=C5[C@]2([C@H]1OC5=C(C=C4)O)CCN3CC6CC6)O)C(=O)/C=C/C7=COC=C7

IUPAC name: (E)-N-[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-(furan-3-yl)-N-methylprop-2-enamide

Also known as: MT-9938, Nalfurafina, Nalfurafine, nalfurafine, NALFURAFINE, NA, Nalfurafine (hydrochloride)

Parent form; salt/anhydrous children: CHEMBL490665

Patent coverage: 157 distinct patent families (310 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 225 (73%) 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
OPRK1	κ receptor	Full agonist	10.1	0%	P41145

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: MAP kinase p38, Mu-type opioid receptor, Delta-type opioid receptor, Kappa-type opioid receptor, Delta-type opioid receptor, Mu-type opioid receptor, Delta-type opioid receptor, Mitogen-activated protein kinase 3, Kappa-type opioid receptor, Kappa-type opioid receptor.

Bioactivity

ChEMBL activities: 31 potent at pChembl ≥ 5 of 31 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
OPRK1	10.72	Ki	0.02	nM	CHEMBL_ACT_24795898
OPRK1	10.6	EC50	0.03	nM	CHEMBL_ACT_2085890
OPRK1	10.47	EC50	0.03	nM	CHEMBL_ACT_15763080
P33534	10.44	IC50	0.04	nM	CHEMBL_ACT_25611603
OPRK1	10.3	EC50	0.05	nM	CHEMBL_ACT_15139366
P41144	9.77	Ki	0.17	nM	CHEMBL_ACT_15763036
P41144	9.74	Ki	0.18	nM	CHEMBL_ACT_15139342
P41144	9.65	Ki	0.23	nM	CHEMBL_ACT_3412720
P41144	9.65	Ki	0.23	nM	CHEMBL_ACT_5234097
OPRK1	9.64	Ki	0.23	nM	CHEMBL_ACT_10857905
OPRK1	9.64	Ki	0.23	nM	CHEMBL_ACT_13318933
P33533	9.43	Ki	0.37	nM	CHEMBL_ACT_15763059
P97266	9.41	Ki	0.39	nM	CHEMBL_ACT_15763047
P42866	9.37	Ki	0.43	nM	CHEMBL_ACT_15139327
P34975	9.3	EC50	0.5	nM	CHEMBL_ACT_19114954
MAPK1	9.26	EC50	0.55	nM	CHEMBL_ACT_19281589
MAPK3	9.26	EC50	0.55	nM	CHEMBL_ACT_19281590
P97266	9.23	Ki	0.58	nM	CHEMBL_ACT_3412730
P97266	9.23	Ki	0.58	nM	CHEMBL_ACT_5234126
OPRM1	9.15	Ki	0.7	nM	CHEMBL_ACT_24795892
OPRM1	9.14	EC50	0.72	nM	CHEMBL_ACT_15139360
OPRK1	8.85	EC50	1.4	nM	CHEMBL_ACT_19114956
P34975	8.28	EC50	5.2	nM	CHEMBL_ACT_19114950
MAPK13	8.28	EC50	5.2	nM	CHEMBL_ACT_19281588
OPRD1	7.44	Ki	36.5	nM	CHEMBL_ACT_24795904
P32300	7.29	Ki	51.3	nM	CHEMBL_ACT_15139316
OPRD1	7.13	EC50	74.1	nM	CHEMBL_ACT_15139363
HCRTR1	7.08	IC50	82.8	nM	CHEMBL_ACT_27725333
OPRK1	6.96	EC50	110	nM	CHEMBL_ACT_19114952
OPRK1	6.77	Ki	170	nM	CHEMBL_ACT_15763024

Target pathways

Aggregated over 1 target gene(s): OPRK1.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	1	OPRK1
G alpha (i) signalling events	1	OPRK1
MECP2 regulates neuronal receptors and channels	1	OPRK1

Dominant GO biological processes

GO term	Targets
immune response	1
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
neuropeptide signaling pathway	1
chemical synaptic transmission	1
sensory perception	1
locomotory behavior	1
sensory perception of pain	1
adenylate cyclase-inhibiting opioid receptor signaling pathway	1
response to insulin	1
positive regulation of dopamine secretion	1
negative regulation of luteinizing hormone secretion	1
response to nicotine	1
G protein-coupled opioid receptor signaling pathway	1
maternal behavior	1

Indications & clinical

Indications

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 6.

Phase distribution

Phase	Trials
PHASE3	2
PHASE2	2
PHASE4	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07380113	PHASE4	NOT_YET_RECRUITING	Anrikefon vs Nalfurafine for Sleep Quality in Hemodialysis Patients With CKD-aP
NCT00793156	PHASE3	UNKNOWN	A Randomized-Withdrawal Phase 3 Study Evaluating the Safety and Efficacy of Oral Nalfurafine HCl (AC-820)in Subjects on Hemodialysis With Uremic Pruritus (Renal Itch)
NCT01513161	PHASE3	COMPLETED	Efficacy and Safety Study of TRK-820 to Treat Conventional-treatment-resistant Pruritus in Patients Receiving Hemodialysis
NCT00638495	PHASE2	COMPLETED	Phase II Study of TRK-820 Soft Capsules - Intractable Pruritus in Patients With Chronic Liver Disease -
NCT01660243	PHASE2	TERMINATED	Efficacy and Safety of MT-9938 for Treatment of Uremic Pruritus in Subjects With End-stage Renal Disease Receiving Hemodialysis
NCT07478133	Not specified	COMPLETED	Bioequivalence Study of Nalfurafine Hydrochloride Orally Disintegrating Tablets on Fasting and Fed in Humans

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.

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

Molecule	Source	Status	Shared targets
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	OPRK1
ALOGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	OPRK1
PROPOXYPHENE	ChEMBL + PubChem	Phase 4 (approved)	OPRK1
ACRIVASTINE	ChEMBL	Phase 4 (approved)	OPRK1
ALMITRINE	ChEMBL	Phase 4 (approved)	OPRK1
ALPIDEM	ChEMBL	Phase 4 (approved)	OPRK1
ALPRAZOLAM	ChEMBL	Phase 4 (approved)	OPRK1
ALVIMOPAN	ChEMBL	Phase 4 (approved)	OPRK1
AMBENONIUM	ChEMBL	Phase 4 (approved)	OPRK1
AMIODARONE	ChEMBL	Phase 4 (approved)	OPRK1
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	OPRK1
AMLODIPINE	ChEMBL	Phase 4 (approved)	OPRK1
AMOXAPINE	ChEMBL	Phase 4 (approved)	OPRK1
AMSACRINE	ChEMBL	Phase 4 (approved)	OPRK1
APOMORPHINE	ChEMBL	Phase 4 (approved)	OPRK1
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	OPRK1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	OPRK1
ATAZANAVIR	ChEMBL	Phase 4 (approved)	OPRK1
ATOMOXETINE	ChEMBL	Phase 4 (approved)	OPRK1
ATRACURIUM	ChEMBL	Phase 4 (approved)	OPRK1
AZATADINE	ChEMBL	Phase 4 (approved)	OPRK1
BACAMPICILLIN	ChEMBL	Phase 4 (approved)	OPRK1
BECLOBRATE	ChEMBL	Phase 4 (approved)	OPRK1
BENPERIDOL	ChEMBL	Phase 4 (approved)	OPRK1
BENZNIDAZOLE	ChEMBL	Phase 4 (approved)	OPRK1
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	OPRK1
BENZTROPINE	ChEMBL	Phase 4 (approved)	OPRK1
BEPRIDIL	ChEMBL	Phase 4 (approved)	OPRK1
BIFONAZOLE	ChEMBL	Phase 4 (approved)	OPRK1
BISACODYL	ChEMBL	Phase 4 (approved)	OPRK1
BOSUTINIB	ChEMBL	Phase 4 (approved)	OPRK1
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	OPRK1
BROMPERIDOL	ChEMBL	Phase 4 (approved)	OPRK1
BUCLIZINE	ChEMBL	Phase 4 (approved)	OPRK1
BUFLOMEDIL	ChEMBL	Phase 4 (approved)	OPRK1
BUPRENORPHINE	ChEMBL	Phase 4 (approved)	OPRK1
BUPROPION	ChEMBL	Phase 4 (approved)	OPRK1
BUTOCONAZOLE	ChEMBL	Phase 4 (approved)	OPRK1
BUTORPHANOL	ChEMBL	Phase 4 (approved)	OPRK1
CALCITRIOL	ChEMBL	Phase 4 (approved)	OPRK1
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	OPRK1
CANNABIDIOL	ChEMBL	Phase 4 (approved)	OPRK1
CANRENONE	ChEMBL	Phase 4 (approved)	OPRK1
CARTEOLOL	ChEMBL	Phase 4 (approved)	OPRK1
CARVEDILOL	ChEMBL	Phase 4 (approved)	OPRK1
CHLOPHEDIANOL	ChEMBL	Phase 4 (approved)	OPRK1
CHLORDIAZEPOXIDE	ChEMBL	Phase 4 (approved)	OPRK1
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	OPRK1
CHLOROXINE	ChEMBL	Phase 4 (approved)	OPRK1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	OPRK1
CICLESONIDE	ChEMBL	Phase 4 (approved)	OPRK1
CILOSTAZOL	ChEMBL	Phase 4 (approved)	OPRK1
CINACALCET	ChEMBL	Phase 4 (approved)	OPRK1
CINNARIZINE	ChEMBL	Phase 4 (approved)	OPRK1
CISAPRIDE	ChEMBL	Phase 4 (approved)	OPRK1
CLEMASTINE	ChEMBL	Phase 4 (approved)	OPRK1
CLIOQUINOL	ChEMBL	Phase 4 (approved)	OPRK1
CLOBAZAM	ChEMBL	Phase 4 (approved)	OPRK1
CLOFAZIMINE	ChEMBL	Phase 4 (approved)	OPRK1
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	OPRK1