Nomifensine

Summary

Nomifensine (CHEMBL273575) is an approved small-molecule dopamine uptake inhibitor (ATC N06AX04) targeting SLC6A2 and SLC6A3; indicated across 1 condition including depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AX04
• Targets: 2 (SLC6A2, SLC6A3)
• Indications: 1 condition
• Chemistry: 238.33 Da · C16H18N2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL273575
Name	Nomifensine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	4528
ChEBI	CHEBI:116225
ATC	N06AX04
Molecular formula	C16H18N2
Molecular weight	238.33
InChIKey	XXPANQJNYNUNES-UHFFFAOYSA-N

SMILES: CN1CC(C2=C(C1)C(=CC=C2)N)C3=CC=CC=C3

IUPAC name: 2-methyl-4-phenyl-3,4-dihydro-1H-isoquinolin-8-amine

ChEBI definition: An N-methylated tetrahydroisoquinoline carrying phenyl and amino substituents at positions C-4 and C-8, respectively.

Pharmacological roles (ChEBI): dopamine uptake inhibitor.

Also known as: Linamiphen, Nomifensin, Nomifensina, Nomifensine, SID11111524, SID11112723, SID90340560, nomifensine, SID50100288, SID50105261, rac-Nomifensine, NOMIFENSINE

Parent form; salt/anhydrous children: CHEMBL1256842

Patent coverage: 1,805 distinct patent families (7,327 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 7,284 (99%) 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
SLC6A2	NET	Inhibition	8.1	0.4%	P23975
SLC6A3	DAT	Inhibition		0.2%	Q01959

Broader ChEMBL bioactivity targets: 23 (assay-derived). Sample: Prelamin-A/C, Dopamine receptor, Sodium-dependent noradrenaline transporter, 5-hydroxytryptamine receptor 2A, Sodium-dependent serotonin transporter, Alpha-1A adrenergic receptor, Prostaglandin G/H synthase 2, Histamine H1 receptor, Mu-type opioid receptor, Sodium-dependent dopamine transporter, Voltage-gated inwardly rectifying potassium channel KCNH2, Muscarinic acetylcholine receptor M1, Cytochrome P450 2D6, Sodium-dependent serotonin transporter, Nuclear factor NF-kappa-B p105 subunit, Cytochrome P450 1A2, Sodium-dependent dopamine transporter, Cytochrome P450 3A4, Polyunsaturated fatty acid lipoxygenase ALOX12, Guanine nucleotide-binding protein G(i) subunit alpha-1/Regulator of G-protein signaling 12.

Bioactivity

ChEMBL activities: 58 potent at pChembl ≥ 5 of 75 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
MAPK1	9	Potency	1	nM	CHEMBL_ACT_4548184
SLC6A2	8.42	Ki	3.8	nM	CHEMBL_ACT_18566359
SLC6A2	8.3	Ki	5	nM	CHEMBL_ACT_12652244
SLC6A3	8	Ki	10	nM	CHEMBL_ACT_12652216
SLC6A3	7.82	IC50	15	nM	CHEMBL_ACT_18221608
SLC6A2	7.67	Ki	21.5	nM	CHEMBL_ACT_12169798
SLC6A2	7.64	Ki	23	nM	CHEMBL_ACT_12169811
SLC6A3	7.63	Ki	23.5	nM	CHEMBL_ACT_2439822
P23977	7.58	Ki	26	nM	CHEMBL_ACT_12650855
SLC6A3	7.52	IC50	30.2	nM	CHEMBL_ACT_5129244
SLC6A3	7.5	IC50	31.62	nM	CHEMBL_ACT_5239362
SLC6A3	7.5	IC50	31.62	nM	CHEMBL_ACT_6305165
P23977	7.47	IC50	34	nM	CHEMBL_ACT_343910
SLC6A3	7.37	Ki	43	nM	CHEMBL_ACT_12169762
P23977	7.37	Ki	42.66	nM	CHEMBL_ACT_1244191
P23977	7.34	IC50	46	nM	CHEMBL_ACT_343908
P23977	7.32	IC50	48	nM	CHEMBL_ACT_121510
P18901	7.32	IC50	48	nM	CHEMBL_ACT_437777
P08482	7.15	Potency	70.8	nM	CHEMBL_ACT_4807547
SLC6A3	7.1	Ki	79	nM	CHEMBL_ACT_18566377
P23977	7.1	Ki	79	nM	CHEMBL_ACT_727379
P23977	7.1	Ki	79	nM	CHEMBL_ACT_73086
SLC6A3	7.08	Ki	84	nM	CHEMBL_ACT_12169775
SLC6A2	7.08	Ki	83	nM	CHEMBL_ACT_13336338
SLC6A3	7	AC50	100	nM	CHEMBL_ACT_25124369
SLC6A3	6.96	Ki	109	nM	CHEMBL_ACT_13336358
P23977	6.94	IC50	115	nM	CHEMBL_ACT_343911
P23977	6.92	IC50	120	nM	CHEMBL_ACT_343907
P23977	6.7	IC50	200	nM	CHEMBL_ACT_2531670
P23977	6.62	IC50	240	nM	CHEMBL_ACT_343912
SLC6A3	6.55	IC50	281.8	nM	CHEMBL_ACT_13336359
SLC6A2	6.4	AC50	400	nM	CHEMBL_ACT_25145414
P23977	6.39	IC50	410	nM	CHEMBL_ACT_1281911
P23977	6.37	IC50	430	nM	CHEMBL_ACT_343909
SLC6A2	6.2	IC50	631	nM	CHEMBL_ACT_13336339
P31652	6.08	IC50	830	nM	CHEMBL_ACT_121512
P31652	6.08	IC50	830	nM	CHEMBL_ACT_437779
SLC6A4	6.06	Ki	874	nM	CHEMBL_ACT_18566329
P31652	6.06	Ki	874	nM	CHEMBL_ACT_727381
P31652	6.06	Ki	874	nM	CHEMBL_ACT_73088
SLC6A4	6.03	Ki	935	nM	CHEMBL_ACT_12169727
SLC6A3	5.9	IC50	1255	nM	CHEMBL_ACT_25870950
SLC6A4	5.85	Ki	1400	nM	CHEMBL_ACT_12650997
OPRM1	5.85	AC50	1400	nM	CHEMBL_ACT_25147180
SLC6A4	5.71	Ki	1930	nM	CHEMBL_ACT_13336318
SLC6A4	5.69	Ki	2057	nM	CHEMBL_ACT_12169740
SLC6A4	5.62	AC50	2400	nM	CHEMBL_ACT_25150743
OPRM1	5.36	AC50	4400	nM	CHEMBL_ACT_25157698
KCNH2	5.32	AC50	4800	nM	CHEMBL_ACT_25118468
ALOX12	5.3	Potency	5012	nM	CHEMBL_ACT_4531181
P31652	5.27	IC50	5400	nM	CHEMBL_ACT_1281912
SLC6A3	5.24	IC50	5714	nM	CHEMBL_ACT_25870947
CYP2D6	5.2	Potency	6310	nM	CHEMBL_ACT_4969892
CYP1A2	5.2	AC50	6310	nM	CHEMBL_ACT_6047285
CYP2D6	5.2	AC50	6310	nM	CHEMBL_ACT_6050348
Q63921	5.12	AC50	7500	nM	CHEMBL_ACT_25174808
SLC6A4	5.06	IC50	8710	nM	CHEMBL_ACT_13336319
PTGS2	5	AC50	10000	nM	CHEMBL_ACT_25166592

Target pathways

Aggregated over 2 target gene(s): SLC6A2, SLC6A3.

Top Reactome pathways

14 total, by targets touching each:

Pathway	Targets	Genes
Disease	2	SLC6A2, SLC6A3
Transport of small molecules	2	SLC6A2, SLC6A3
R-HSA-425366	2	SLC6A2, SLC6A3
SLC-mediated transmembrane transport	2	SLC6A2, SLC6A3
SLC-mediated transport of neurotransmitters	2	SLC6A2, SLC6A3
SLC transporter disorders	2	SLC6A2, SLC6A3
Disorders of transmembrane transporters	2	SLC6A2, SLC6A3
Neurotransmitter clearance	1	SLC6A3
Transmission across Chemical Synapses	1	SLC6A3
Neuronal System	1	SLC6A3
Dopamine clearance from the synaptic cleft	1	SLC6A3
Defective neurotransmitter clearance by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)	1	SLC6A3
Defective SLC6A2 causes orthostatic intolerance (OI)	1	SLC6A2
Defective transport of neurotransmitters by SLC6A3 causes Parkinsonism-dystonia infantile (PKDYS)	1	SLC6A3

Dominant GO biological processes

GO term	Targets
neurotransmitter transport	2
amino acid transport	2
response to xenobiotic stimulus	2
obsolete monoamine transport	2
sodium ion transmembrane transport	2
dopamine uptake involved in synaptic transmission	2
norepinephrine uptake	2
transmembrane transport	2
chemical synaptic transmission	1
obsolete norepinephrine transport	1
response to pain	1
neuron cellular homeostasis	1
catecholamine uptake	1
neurotransmitter reuptake	1
chloride transmembrane transport	1

Indications & clinical

Indications

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

Indication	Phase	MONDO	EFO
depressive disorder	4	MONDO:0002050	MONDO:0002009

Clinical trials

Total trials: 0.

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.

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

Molecule	Source	Status	Shared targets
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
Idelalisib	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
Olodaterol	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
TAFENOQUINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
UMECLIDINIUM	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A3
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
AMINOCAPROIC ACID	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
AMIODARONE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
AMLODIPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
AMODIAQUINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
AMOXAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
ASENAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
ATOMOXETINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
AZELASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BENFLUOREX	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BENOXINATE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BENPERIDOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BENZIODARONE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BENZTROPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BENZYDAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BENZYL BENZOATE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BEPRIDIL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BEXAROTENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BITHIONOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BOSUTINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BROMHEXINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BROMPERIDOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
BUPROPION	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CABERGOLINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CALCITRIOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CANNABIDIOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CARBINOXAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CARVEDILOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CASPOFUNGIN	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CELECOXIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CETIRIZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CHLORPHENTERMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CINACALCET	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CINNARIZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CITALOPRAM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CLEMASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CLOMIPHENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
COBIMETINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
COCAINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CYCLOFENIL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DABIGATRAN ETEXILATE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DANAZOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DASATINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DEQUALINIUM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DESIPRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DESLORATADINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DESOGESTREL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DESVENLAFAXINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DEXBROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DEXCHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DEXTROAMPHETAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DIMENHYDRINATE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DIPHENYLPYRALINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DISULFIRAM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DOBUTAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DOMPERIDONE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DONEPEZIL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DOPAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DOTHIEPIN	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DOXAZOSIN	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DRONEDARONE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DULOXETINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
DYCLONINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
EBASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
ECONAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
EFAVIRENZ	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
ELETRIPTAN	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
EPALRESTAT	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
ERDAFITINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3
ERYTHROMYCIN PROPIONATE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A3