Protriptyline

Summary

Protriptyline (CHEMBL668) is an approved small-molecule antidepressant (ATC N06AA11) targeting SLC6A2 and SLC6A4; indicated across 1 condition including depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N06AA11
• Targets: 2 (SLC6A2, SLC6A4)
• Indications: 1 condition
• Clinical trials: 1
• Chemistry: 263.4 Da · C19H21N

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL668
Name	Protriptyline
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	4976
ChEBI	CHEBI:8597
ATC	N06AA11
Molecular formula	C19H21N
Molecular weight	263.4
InChIKey	BWPIARFWQZKAIA-UHFFFAOYSA-N

SMILES: CNCCCC1C2=CC=CC=C2C=CC3=CC=CC=C13

IUPAC name: N-methyl-3-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenyl)propan-1-amine

Pharmacological roles (ChEBI): antidepressant.

Also known as: Protriptilina, Protriptyline, protriptyline, SID11111679, SID11111680, SID90341254, SID50100330, SID50104299, PROTRIPTYLINE, Protryptyline

Parent form; salt/anhydrous children: CHEMBL1200332

Patent coverage: 4,920 distinct patent families (19,348 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 19,209 (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	8.17	0.4%	P23975
SLC6A4	SERT	Inhibition	7.71	0.7%	P31645

Broader ChEMBL bioactivity targets: 26 (assay-derived). Sample: Lysine-specific demethylase 4E, Prelamin-A/C, Thrombopoietin, 5-hydroxytryptamine receptor 2B, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Muscarinic acetylcholine receptor M2, Muscarinic acetylcholine receptor M1, D(2) dopamine receptor, Sodium-dependent noradrenaline transporter.

Bioactivity

ChEMBL activities: 45 potent at pChembl ≥ 5 of 56 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
SLC6A2	8.96	IC50	1.1	nM	CHEMBL_ACT_1611137
SLC6A2	8.85	Kd	1.4	nM	CHEMBL_ACT_3554433
SLC6A2	8.8	Ki	1.6	nM	CHEMBL_ACT_13341984
SLC6A2	8.77	IC50	1.7	nM	CHEMBL_ACT_10899066
SLC6A2	8.7	Ki	2	nM	CHEMBL_ACT_10899108
SLC6A2	8.7	Ki	2	nM	CHEMBL_ACT_26333223
SLC6A2	8.68	IC50	2.1	nM	CHEMBL_ACT_13342056
SLC6A2	8.68	Ki	2.1	nM	CHEMBL_ACT_17995199
SLC6A2	8.64	Ki	2.3	nM	CHEMBL_ACT_6317050
SLC6A2	8.6	IC50	2.5	nM	CHEMBL_ACT_13336154
SLC6A2	8.57	IC50	2.7	nM	CHEMBL_ACT_26333168
SLC6A2	8.55	IC50	2.8	nM	CHEMBL_ACT_16501779
SLC6A2	8.55	IC50	2.8	nM	CHEMBL_ACT_16838469
SLC6A2	8.54	IC50	2.9	nM	CHEMBL_ACT_17995184
SLC6A2	8.17	Ki	6.8	nM	CHEMBL_ACT_2381339
SLC6A2	8.15	IC50	7.1	nM	CHEMBL_ACT_2573352
LMNA	8.15	Potency	7.1	nM	CHEMBL_ACT_3651629
SLC6A2	8.04	IC50	9.1	nM	CHEMBL_ACT_2381313
SLC6A2	7.77	IC50	17	nM	CHEMBL_ACT_5165964
HRH1	7.3	AC50	50	nM	CHEMBL_ACT_25212156
P08482	6.8	Potency	158.5	nM	CHEMBL_ACT_4807447
CHRM3	6.62	AC50	240	nM	CHEMBL_ACT_25136356
P08482	6.4	Potency	398.1	nM	CHEMBL_ACT_4857774
ADRA1A	6.34	AC50	460.7	nM	CHEMBL_ACT_25137723
CHRM1	6.24	AC50	570	nM	CHEMBL_ACT_25135096
CHRM2	6.18	AC50	653.5	nM	CHEMBL_ACT_25195178
DRD3	6.07	AC50	850	nM	CHEMBL_ACT_25193182
KCNH2	6	AC50	1004	nM	CHEMBL_ACT_25117337
CHRM2	5.75	AC50	1800	nM	CHEMBL_ACT_25213406
HTR2A	5.75	AC50	1800	nM	CHEMBL_ACT_25224851

Target pathways

Aggregated over 2 target gene(s): SLC6A2, SLC6A4.

Top Reactome pathways

12 total, by targets touching each:

Pathway	Targets	Genes
SLC-mediated transport of neurotransmitters	2	SLC6A2, SLC6A4
Neurotransmitter clearance	1	SLC6A4
Transmission across Chemical Synapses	1	SLC6A4
Neuronal System	1	SLC6A4
Disease	1	SLC6A2
Serotonin clearance from the synaptic cleft	1	SLC6A4
Transport of small molecules	1	SLC6A2
R-HSA-425366	1	SLC6A2
SLC-mediated transmembrane transport	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
neurotransmitter transport	2
amino acid transport	2
response to xenobiotic stimulus	2
obsolete monoamine transport	2
sodium ion transmembrane transport	2
transmembrane transport	2
neurotransmitter reuptake	2
chemical synaptic transmission	1
obsolete norepinephrine transport	1
response to pain	1
dopamine uptake involved in synaptic transmission	1
norepinephrine uptake	1
neuron cellular homeostasis	1
catecholamine uptake	1
chloride transmembrane transport	1

Indications & clinical

Indications

1 indication (1 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:0002009

Clinical trials

Total trials: 1.

Phase distribution

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00754962	Not specified	COMPLETED	Bioequivalency Study of Protriptyline 10 mg Tablets Under Fasted Conditions

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
AMITRIPTYLINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
Olodaterol	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
PIMAVANSERIN	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
Tadalafil	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
TAFENOQUINE	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
UMECLIDINIUM	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
VORAPAXAR	ChEMBL + PubChem	Phase 4 (approved)	SLC6A2, SLC6A4
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ALECTINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
AMBENONIUM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
AMIODARONE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
AMOXAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ASENAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ATOMOXETINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
ATRACURIUM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
AZELASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BENFLUOREX	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BENZPHETAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BENZTROPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BENZYDAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BEPRIDIL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BOSUTINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BROMHEXINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BROMODIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BROMPERIDOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BROMPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BUPROPION	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
BUTENAFINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CABERGOLINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CALCIPOTRIENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CALCITRIOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CARBINOXAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CARVEDILOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CELECOXIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CETIRIZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORPHENTERMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CINACALCET	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CINNARIZINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CITALOPRAM	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CLEMASTINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CLOMIPHENE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CLOZAPINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
COBIMETINIB	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
COCAINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4
DANAZOL	ChEMBL	Phase 4 (approved)	SLC6A2, SLC6A4