Sumatriptan

Summary

Sumatriptan (CHEMBL128) is an approved small-molecule serotonergic agonist (ATC N02CC01) targeting HTR5A, HTR6, and HTR7; indicated across 5 conditions including migraine disorder and migraine with aura.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N02CC01
• Targets: 8 (HTR5A, HTR6, HTR7…)
• Indications: 5 conditions
• Clinical trials: 68
• Chemistry: 295.4 Da · C14H21N3O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL128
Name	Sumatriptan
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5358
ChEBI	CHEBI:10650
ATC	N02CC01
Molecular formula	C14H21N3O2S
Molecular weight	295.4
InChIKey	KQKPFRSPSRPDEB-UHFFFAOYSA-N

SMILES: CNS(=O)(=O)CC1=CC2=C(C=C1)NC=C2CCN(C)C

IUPAC name: 1-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]-N-methylmethanesulfonamide

ChEBI definition: A sulfonamide that consists of N,N-dimethyltryptamine bearing an additional (N-methylsulfamoyl)methyl substituent at position 5. Selective agonist for a vascular 5-HT1 receptor subtype (probably a member of the 5-HT1D family). Used (in the form of its succinate salt) for the acute treatment of migraine with or without aura in adults.

Pharmacological roles (ChEBI): serotonergic agonist, vasoconstrictor agent.

Also known as: Dfn-11, Dfn-11 (sumatriptan injection), Imitrex, N02CC01, Sumatriptan, Tosymra, sumatriptan, SID49679316, SUMATRIPTAN, SID174006309, SID144205081, SID170465377

Parent form; salt/anhydrous children: CHEMBL1201150

Patent coverage: 8,010 distinct patent families (28,367 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 28,313 (100%) 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
HTR5A	5-HT5A receptor	Full agonist	5.3	0%	P47898
HTR6	5-HT6 receptor	Antagonist	5.6	0.2%	P50406
HTR7	5-HT7 receptor	Antagonist	6	0.8%	P34969
HTR1A	5-HT1A receptor	Full agonist	6	0%	P08908
HTR1B	5-HT1B receptor	Partial agonist	8.1	0.2%	P28222
HTR1D	5-HT1D receptor	Full agonist	8.7	0%	P28221
HTR1E	5-ht1e receptor	Full agonist	5.8	0%	P28566
HTR1F	5-HT1F receptor	Full agonist	7.2	0.1%	P30939

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: Multidrug and toxin extrusion protein 1, 5-hydroxytryptamine receptor 1F, 5-hydroxytryptamine receptor 2B, 5-hydroxytryptamine receptor 1B, 5-hydroxytryptamine receptor 3A, 5-hydroxytryptamine receptor 1D, Beta-lactamase, 5-hydroxytryptamine receptor 1A, 5-hydroxytryptamine receptor 1E, 5-hydroxytryptamine receptor 2A.

Bioactivity

ChEMBL activities: 99 potent at pChembl ≥ 5 of 105 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR1B	9.3	Ki	0.5	nM	CHEMBL_ACT_25553866
HTR1D	9.3	Ki	0.5	nM	CHEMBL_ACT_25553871
HTR1B	9.3	IC50	0.5	nM	CHEMBL_ACT_371575
HTR1D	8.92	Ki	1.2	nM	CHEMBL_ACT_2348055
HTR1D	8.7	Ki	2	nM	CHEMBL_ACT_953066
HTR1D	8.53	IC50	2.95	nM	CHEMBL_ACT_371576
HTR1D	8.47	Ki	3.4	nM	CHEMBL_ACT_1300421
HTR1D	8.47	Ki	3.4	nM	CHEMBL_ACT_81178
HTR1D	8.37	EC50	4.3	nM	CHEMBL_ACT_756198
HTR1D	8.36	Ki	4.4	nM	CHEMBL_ACT_756195
HTR1D	8.3	IC50	5	nM	CHEMBL_ACT_284508
HTR1D	8.3	IC50	5	nM	CHEMBL_ACT_782114
HTR1D	8.28	EC50	5.3	nM	CHEMBL_ACT_886833
HTR1D	8.26	Ki	5.5	nM	CHEMBL_ACT_1152343
HTR1B	8.26	Ki	5.5	nM	CHEMBL_ACT_276826
HTR1D	8.24	Ki	5.7	nM	CHEMBL_ACT_459543
Q9N2B7	8.19	Ki	6.4	nM	CHEMBL_ACT_953067
HTR1D	8.17	IC50	6.8	nM	CHEMBL_ACT_1200180
HTR1D	8.17	IC50	6.7	nM	CHEMBL_ACT_208804
HTR1D	8.17	IC50	6.7	nM	CHEMBL_ACT_975387
HTR2C	8.14	IC50	7.3	nM	CHEMBL_ACT_284518
HTR1B	8.11	Ki	7.7	nM	CHEMBL_ACT_1300422
HTR1B	8.11	Ki	7.7	nM	CHEMBL_ACT_81179
P28564	8.09	Ki	8.19	nM	CHEMBL_ACT_7822951
HTR1D	8.07	Ki	8.6	nM	CHEMBL_ACT_425315
HTR1D	8.07	Ki	8.5	nM	CHEMBL_ACT_437121
HTR1D	8.07	Ki	8.5	nM	CHEMBL_ACT_464462
HTR1D	8.07	Ki	8.5	nM	CHEMBL_ACT_558655
HTR1B	8.04	Ki	9.1	nM	CHEMBL_ACT_2348103
HTR3A	8.03	IC50	9.3	nM	CHEMBL_ACT_284519

Target pathways

Aggregated over 8 target gene(s): HTR5A, HTR6, HTR7, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F.

Top Reactome pathways

10 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	8	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
Signaling by GPCR	8	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
Class A/1 (Rhodopsin-like receptors)	8	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
Amine ligand-binding receptors	8	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
Serotonin receptors	8	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
GPCR ligand binding	8	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
GPCR downstream signalling	7	HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
G alpha (i) signalling events	5	HTR1B, HTR1D, HTR1E, HTR1F, HTR5A
G alpha (s) signalling events	2	HTR6, HTR7
RHOBTB3 ATPase cycle	1	HTR7

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	8
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	8
chemical synaptic transmission	8
signal transduction	8
adenylate cyclase-inhibiting serotonin receptor signaling pathway	6
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5
G protein-coupled serotonin receptor signaling pathway	4
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	4
vasoconstriction	3
regulation of behavior	3
adenylate cyclase-activating serotonin receptor signaling pathway	2
smooth muscle contraction	2
hippocampus development	1
response to estradiol	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1

Indications & clinical

Indications

5 indications (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
migraine disorder	4	MONDO:0005277	MONDO:0005277
migraine with aura	3	MONDO:0005475	MONDO:0005475
migraine without aura	3	MONDO:0100431	MONDO:0100431
obesity disorder	0	MONDO:0011122	EFO:0001073

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

Clinical trials

Total trials: 68.

Phase distribution

Phase	Trials
Not specified	21
PHASE3	13
PHASE1	13
PHASE4	11
PHASE2	8
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00449787	PHASE4	COMPLETED	Comparing Naproxen to Sumatriptan for Emergency Headache Patients
NCT00792636	PHASE4	COMPLETED	A Study to Determine the Effect of Sumatriptan and Naproxen Sodium Combination Tablet, Sumatriptan Tablet, and Naproxen Sodium Tablet on Blood Pressure When Treating Migraine Headaches That Occur During a 6-month Period
NCT01016834	PHASE4	COMPLETED	Evaluation of Treatment Satisfaction and Preference for Sumavel DosePro in the Treatment of Migraine
NCT01053507	PHASE4	TERMINATED	Treximet for Prevention of Post Traumatic Headache Associated With Cognitive Dysfunction
NCT01071317	PHASE4	COMPLETED	Trial of Comprehensive Migraine Intervention
NCT01090050	PHASE4	COMPLETED	Treximet in the Treatment of Chronic Migraine
NCT01248468	PHASE4	COMPLETED	Efficacy and Safety of Acetaminophen, Aspirin and Caffeine With Sumatriptan in the Acute Treatment of Migraine
NCT01300546	PHASE4	COMPLETED	Treximet Trademark (TM) in the Prevention and Modification of Disease Progression in Migraine
NCT01450995	PHASE4	COMPLETED	Migraine Treatment Satisfaction With Treximet Versus Concomitant 2 Aleve and Imitrex
NCT01807234	PHASE4	COMPLETED	Comparison of Ketorolac Nasal Spray to Sumatriptan Nasal Spray and Placebo for Acute Treatment of Migraine
NCT05108688	PHASE4	COMPLETED	Mirtazapine vs Sumatriptan in the Treatment of Postdural Puncture Headache
NCT00433732	PHASE3	COMPLETED	To Evaluate the Safety and Efficacy of Trexima in the Acute Treatment of Migraine Headaches
NCT00434083	PHASE3	COMPLETED	To Evaluate the Safety and Efficacy of Trexima in the Acute Treatment of Migrane Headaches
NCT00442221	PHASE3	COMPLETED	The Safety Of Combo Formulation In The Treatment Of Multiple Episodes Of Acute Migraine Over 12 Months
NCT00843024	PHASE3	COMPLETED	Migraine Study in Adolescent Patients
NCT00894556	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine (0462-087)
NCT00897104	PHASE3	COMPLETED	MK0462 5 mg, Sumatriptan 50 mg, and Placebo Comparison Study (0462-029)
NCT00898677	PHASE3	COMPLETED	Rizatriptan 5 mg and 10 mg, Sumatriptan 100 mg, and Placebo Comparison Study (0462-030)
NCT00963937	PHASE3	COMPLETED	Study to Evaluate the Efficacy and Safety of Oral Sumatriptan for the Acute Treatment of Migraine in Children and Adolescents
NCT01462812	PHASE3	COMPLETED	Safety & Efficacy of a Single Dose of Sumatriptan Powder Delivered Intranasally With the Bi-directional Device in Adults With Acute Migraine
NCT01814189	PHASE3	COMPLETED	Efficacy and Safety of Oral Sumatriptan Plus Oral Promethazine in Migraine Treatment
NCT01986088	PHASE3	COMPLETED	Eletriptan vs Sumatriptan: A Double-blind, Placebo-controlled, Multiple Migraine Attack Study
NCT01986270	PHASE3	COMPLETED	Comparative Study of Oral Eletriptan (40mg and 80mg), Oral Sumatriptan (25mg and 50mg) and Placebo
NCT02569853	PHASE3	COMPLETED	DFN-11 Injection in Episodic Migraine With or Without Aura
NCT03185143	PHASE2/PHASE3	COMPLETED	Low-Dose Naltrexone and Acetaminophen Combination and Sumatriptan in the Acute Treatment of Migraine With Nausea
NCT00530517	PHASE2	COMPLETED	A Study on the Usability of the Needle-free Intraject® System in Adult Patients During Acute Migraine Attack
NCT00804973	PHASE2	TERMINATED	Study in Participants With Acute Migraines Headaches
NCT00892203	PHASE2	COMPLETED	Efficacy and Safety of BGG492 in the Treatment of Migraine
NCT01430442	PHASE2	COMPLETED	Dose Ranging Study of Rimegepant (BMS-927711) for the Acute Treatment of Migraine
NCT01791400	PHASE2	COMPLETED	Effect of Metoclopramide Versus Sumatriptan for Emergency Department Treatment of Migraine Headache
NCT01854385	PHASE2	COMPLETED	Sumatriptan as Treatment for Post-traumatic Headache
NCT02571049	PHASE2	COMPLETED	Pilot Study of Two Different Strengths of DFN-11 Injection for Rapidly Escalating Migraine
NCT02583425	PHASE2	TERMINATED	Pilot Study of DFN-11 Injection in Medication Overuse Headache
NCT00620425	PHASE1	COMPLETED	A Study on the Effects of Repeat Doses of Intraject® Sumatriptan on Local Site Signs
NCT00701389	PHASE1	COMPLETED	Study to Evaluate the Safety, Tolerability, and Blood Pressure Effect of an Oral Dose of Sumatriptan Alone and in Combination With MK-0974 (Telcagepant) in Migraine Patients (0974-026)
NCT01269281	PHASE1	COMPLETED	Bioequivalence Study of Sumatriptan Succinate Tablets 100 mg in Fed Conditions
NCT01507610	PHASE1	COMPLETED	Bioavailability Study to Compare OPTINOSE SUMATRIPTAN With IMITREX® in Healthy Subjects
NCT01579383	PHASE1	COMPLETED	Safety Tolerability and Pharmacokinetics of ALD403
NCT02741310	PHASE1	COMPLETED	Study to Evaluate the Effect of Erenumab on Blood Pressure When Given Concomitantly With Subcutaneous Sumatriptan
NCT02932488	PHASE1	TERMINATED	Cerebral Pharmacodynamic Effects of 5-HT1B Receptor Stimulation

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 8 clinical and 29 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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
SEROTONIN	ChEMBL + PubChem	Phase 3 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
MEBUFOTENIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6, HTR7
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR5A, HTR6, HTR7
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1E, HTR1F, HTR5A, HTR6, HTR7
ERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR5A, HTR6
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1E, HTR1F, HTR5A, HTR6, HTR7
PSILOCIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR1E, HTR5A, HTR6, HTR7
Cyproheptadine	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F, HTR5A, HTR6, HTR7
SORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F, HTR5A, HTR6, HTR7
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
KETANSERIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
NEFAZODONE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR5A, HTR6, HTR7
YOHIMBINE	ChEMBL + PubChem	Phase 3 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR6
LYSERGIDE	ChEMBL	Phase 2	HTR1A, HTR1D, HTR1E, HTR5A, HTR6, HTR7
RITANSERIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1E, HTR5A, HTR6, HTR7
Lasmiditan	ChEMBL + PubChem	Phase 4 (approved)	HTR1D, HTR1E, HTR1F, HTR5A, HTR7
NARATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Pramipexole	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1E, HTR5A, HTR7
QUETIAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F, HTR6, HTR7
RIZATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
TEGASEROD	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1D, HTR5A, HTR6, HTR7
ZOLMITRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR1B, HTR1D, HTR1E, HTR6, HTR7
CINACALCET	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D, HTR5A, HTR6, HTR7
FROVATRIPTAN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR7
VILAZODONE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR6, HTR7
LATREPIRDINE	ChEMBL	Phase 3	HTR1D, HTR1E, HTR5A, HTR6, HTR7
NIGULDIPINE	ChEMBL	Phase 2	HTR1A, HTR1B, HTR5A, HTR6, HTR7
PENFLURIDOL	ChEMBL	Phase 2	HTR1A, HTR1D, HTR5A, HTR6, HTR7
AMOXAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7
DOXEPIN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7
ELETRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1E, HTR1F
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7
LOXAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7
METHYLERGONOVINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR1F, HTR6
ZIPRASIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR6, HTR7
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7
MIANSERIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1D, HTR6, HTR7
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR6
PROMAZINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR5A, HTR6, HTR7
SALMETEROL	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR7
SILODOSIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR7
FANANSERIN	ChEMBL	Phase 2	HTR1A, HTR5A, HTR6, HTR7
GSK163090	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR7
METITEPINE	ChEMBL	Phase 2	HTR1A, HTR5A, HTR6, HTR7
SPIPERONE	ChEMBL	Phase 2	HTR1A, HTR5A, HTR6, HTR7
SPIRAMIDE	ChEMBL	Phase 2	HTR1A, HTR1D, HTR6, HTR7
ASENAPINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1E, HTR6
HYDROXYZINE	ChEMBL + PubChem	Phase 4 (approved)	HTR5A, HTR6, HTR7
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HTR1B, HTR1D, HTR7
PAROXETINE	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR5A, HTR6
CARVEDILOL	ChEMBL	Phase 4 (approved)	HTR1A, HTR6, HTR7
DIBENZEPIN	ChEMBL	Phase 4 (approved)	HTR1A, HTR6, HTR7
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	HTR1A, HTR6, HTR7
IPRINDOLE	ChEMBL	Phase 4 (approved)	HTR1A, HTR5A, HTR6