Maprotiline

Summary

Maprotiline (CHEMBL21731) is an approved small molecule (ATC N06AA21) targeting KCNJ6, KCNJ5, and TRPM3; indicated across 7 conditions including depressive disorder and anxiety.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AA21
• Targets: 4 (KCNJ6, KCNJ5, TRPM3…)
• Indications: 7 conditions
• Clinical trials: 2
• Chemistry: 277.4 Da · C20H23N

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL21731
Name	Maprotiline
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	4011
ATC	N06AA21
Molecular formula	C20H23N
Molecular weight	277.4
InChIKey	QSLMDECMDJKHMQ-UHFFFAOYSA-N

SMILES: CNCCCC12CCC(C3=CC=CC=C31)C4=CC=CC=C24

IUPAC name: N-methyl-3-(1-tetracyclo[6.6.2.02,7.09,14]hexadeca-2,4,6,9,11,13-hexaenyl)propan-1-amine

Also known as: BA-34,276 FREE BASE, BA-34,276 [AS HYDROCHLORIDE], BA-34276 FREE BASE, Maprotilina, Maprotiline, maprotilline, maprotiline, SID11111502, SID11112599, SID11113802, SID50085871, SID90341780

Parent form; salt/anhydrous children: CHEMBL1237135

Patent coverage: 5,311 distinct patent families (19,686 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 19,226 (98%) 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
KCNJ6	Kir3.2	Antagonist	4	0.1%	P48051
KCNJ5	Kir3.4	Antagonist	3.5	0%	P48544
TRPM3	TRPM3		5.8	0.1%	Q9HCF6
SLC6A2	NET	Inhibition	7.92	0.4%	P23975

Broader ChEMBL bioactivity targets: 48 (assay-derived). Sample: Lysine-specific demethylase 4E, Nuclear receptor ROR-gamma, Inositol monophosphatase 1, Thrombopoietin, NPC intracellular cholesterol transporter 1, Ras-related protein Rab-9A, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, D(1B) dopamine receptor, Alpha-2A adrenergic receptor.

Bioactivity

ChEMBL activities: 84 potent at pChembl ≥ 5 of 111 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HRH1	8.99	Ki	1.02	nM	CHEMBL_ACT_7749096
HRH1	8.78	Ki	1.67	nM	CHEMBL_ACT_2600996
HRH1	8.1	AC50	7.9	nM	CHEMBL_ACT_25212154
HRH1	8.06	IC50	8.79	nM	CHEMBL_ACT_7749095
SLC6A2	7.92	Ki	12	nM	CHEMBL_ACT_3066016
HTR2A	7.75	Ki	18	nM	CHEMBL_ACT_7751215
SLC6A2	7.52	IC50	30	nM	CHEMBL_ACT_7747007
SLC6A2	7.52	Ki	30	nM	CHEMBL_ACT_7747008
HTR2C	7.39	Ki	41	nM	CHEMBL_ACT_7751219
CHRM4	7.24	Ki	58	nM	CHEMBL_ACT_7749130
HTR2A	7.19	IC50	64	nM	CHEMBL_ACT_7751214
HTR2C	7.11	IC50	78	nM	CHEMBL_ACT_7751218
P15823	7.05	Ki	90	nM	CHEMBL_ACT_7746992
CHRM3	7	Ki	100	nM	CHEMBL_ACT_7749128
CHRM5	6.94	Ki	115	nM	CHEMBL_ACT_7749132
ADRA2B	6.88	Ki	133	nM	CHEMBL_ACT_7746998
CHRM1	6.84	Ki	143	nM	CHEMBL_ACT_7749124
CHRM5	6.8	IC50	160	nM	CHEMBL_ACT_7749131
P15823	6.79	IC50	163	nM	CHEMBL_ACT_7746991
SLC6A2	6.77	AC50	170	nM	CHEMBL_ACT_25144652
DRD1	6.73	Ki	187	nM	CHEMBL_ACT_7749062
ADRA1D	6.71	Ki	195	nM	CHEMBL_ACT_7746994
HTR2B	6.67	Ki	214	nM	CHEMBL_ACT_7751217
DRD3	6.66	Ki	219	nM	CHEMBL_ACT_7749066
P43140	6.64	Ki	230	nM	CHEMBL_ACT_7746990
ADRA2B	6.54	IC50	292	nM	CHEMBL_ACT_7746997
HTR2B	6.47	IC50	336	nM	CHEMBL_ACT_7751216
DRD1	6.43	IC50	373	nM	CHEMBL_ACT_7749061
HRH2	6.41	Ki	393	nM	CHEMBL_ACT_7749098
DRD1	6.4	Ki	402	nM	CHEMBL_ACT_2601010

Target pathways

Aggregated over 4 target gene(s): KCNJ6, KCNJ5, TRPM3, SLC6A2.

Top Reactome pathways

20 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter receptors and postsynaptic signal transmission	2	KCNJ5, KCNJ6
Transmission across Chemical Synapses	2	KCNJ5, KCNJ6
Neuronal System	2	KCNJ5, KCNJ6
Activation of G protein gated Potassium channels	2	KCNJ5, KCNJ6
G protein gated Potassium channels	2	KCNJ5, KCNJ6
Inwardly rectifying K+ channels	2	KCNJ5, KCNJ6
Potassium Channels	2	KCNJ5, KCNJ6
GABA receptor activation	2	KCNJ5, KCNJ6
GABA B receptor activation	2	KCNJ5, KCNJ6
Activation of GABAB receptors	2	KCNJ5, KCNJ6
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	2	KCNJ5, KCNJ6
Disease	1	SLC6A2
TRP channels	1	TRPM3
Transport of small molecules	1	SLC6A2
R-HSA-425366	1	SLC6A2
SLC-mediated transmembrane transport	1	SLC6A2
SLC-mediated transport of neurotransmitters	1	SLC6A2
SLC transporter disorders	1	SLC6A2
Defective SLC6A2 causes orthostatic intolerance (OI)	1	SLC6A2
Disorders of transmembrane transporters	1	SLC6A2

Dominant GO biological processes

GO term	Targets
monoatomic ion transport	3
monoatomic ion transmembrane transport	3
potassium ion transport	2
regulation of monoatomic ion transmembrane transport	2
potassium ion import across plasma membrane	2
monoatomic cation transmembrane transport	2
transmembrane transport	2
potassium ion transmembrane transport	1
regulation of heart rate by cardiac conduction	1
membrane repolarization during atrial cardiac muscle cell action potential	1
ventricular cardiac muscle cell membrane repolarization	1
membrane repolarization during ventricular cardiac muscle cell action potential	1
monoatomic cation transport	1
calcium ion transport	1
protein homotetramerization	1

Indications & clinical

Indications

7 indications (2 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
depressive disorder	4	MONDO:0002050	MONDO:0002050
anxiety	3	MONDO:0011918	EFO:0005230
dementia	3	MONDO:0001627	HP:0000726
glioblastoma	1	MONDO:0018177	EFO:0000519
brain neoplasm	1	MONDO:0021211	EFO:0003833

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

Clinical trials

Total trials: 2.

Phase distribution

Phase	Trials
PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients
NCT04200066	PHASE1	WITHDRAWN	A Study of Maprotiline in Combination With Tamoxifen and Temozolomide for Recurrent Glioblastoma

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 5 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

Molecule	Source	Status	Shared targets
Imipramine	ChEMBL + PubChem	Phase 4 (approved)	KCNJ5, SLC6A2
Mefloquine	ChEMBL + PubChem	Phase 4 (approved)	KCNJ5, SLC6A2
Propafenone	ChEMBL + PubChem	Phase 4 (approved)	KCNJ5, SLC6A2
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
DACOMITINIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
TAFENOQUINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
UMECLIDINIUM	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	SLC6A2
ALECTINIB	ChEMBL	Phase 4 (approved)	SLC6A2
ALFACALCIDOL	ChEMBL	Phase 4 (approved)	SLC6A2
ALFUZOSIN	ChEMBL	Phase 4 (approved)	SLC6A2
AMBENONIUM	ChEMBL	Phase 4 (approved)	SLC6A2
AMINOCAPROIC ACID	ChEMBL	Phase 4 (approved)	SLC6A2
AMIODARONE	ChEMBL	Phase 4 (approved)	SLC6A2
AMLODIPINE	ChEMBL	Phase 4 (approved)	SLC6A2
AMODIAQUINE	ChEMBL	Phase 4 (approved)	SLC6A2
AMOXAPINE	ChEMBL	Phase 4 (approved)	SLC6A2
AMPHETAMINE	ChEMBL	Phase 4 (approved)	SLC6A2
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2
ASENAPINE	ChEMBL	Phase 4 (approved)	SLC6A2
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	SLC6A2
ATOMOXETINE	ChEMBL	Phase 4 (approved)	SLC6A2
ATRACURIUM	ChEMBL	Phase 4 (approved)	SLC6A2
AZELASTINE	ChEMBL	Phase 4 (approved)	SLC6A2
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	SLC6A2
BENFLUOREX	ChEMBL	Phase 4 (approved)	SLC6A2
BENOXINATE	ChEMBL	Phase 4 (approved)	SLC6A2
BENPERIDOL	ChEMBL	Phase 4 (approved)	SLC6A2
BENZIODARONE	ChEMBL	Phase 4 (approved)	SLC6A2
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	SLC6A2
BENZTROPINE	ChEMBL	Phase 4 (approved)	SLC6A2
BENZYDAMINE	ChEMBL	Phase 4 (approved)	SLC6A2
BENZYL BENZOATE	ChEMBL	Phase 4 (approved)	SLC6A2
BEPRIDIL	ChEMBL	Phase 4 (approved)	SLC6A2
BEXAROTENE	ChEMBL	Phase 4 (approved)	SLC6A2
BITHIONOL	ChEMBL	Phase 4 (approved)	SLC6A2
BOSUTINIB	ChEMBL	Phase 4 (approved)	SLC6A2
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2
BROMHEXINE	ChEMBL	Phase 4 (approved)	SLC6A2
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2
BROMPERIDOL	ChEMBL	Phase 4 (approved)	SLC6A2
BROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2
BUPROPION	ChEMBL	Phase 4 (approved)	SLC6A2
BUTENAFINE	ChEMBL	Phase 4 (approved)	SLC6A2
CABERGOLINE	ChEMBL	Phase 4 (approved)	SLC6A2
CALCIPOTRIENE	ChEMBL	Phase 4 (approved)	SLC6A2
CALCITRIOL	ChEMBL	Phase 4 (approved)	SLC6A2
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	SLC6A2
CANNABIDIOL	ChEMBL	Phase 4 (approved)	SLC6A2
CARBINOXAMINE	ChEMBL	Phase 4 (approved)	SLC6A2
CARVEDILOL	ChEMBL	Phase 4 (approved)	SLC6A2
CASPOFUNGIN	ChEMBL	Phase 4 (approved)	SLC6A2
CELECOXIB	ChEMBL	Phase 4 (approved)	SLC6A2
CETIRIZINE	ChEMBL	Phase 4 (approved)	SLC6A2
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	SLC6A2