Ulotaront
drugOn this page
Also known as Sep-363856SEP-856
Summary
Ulotaront (CHEMBL4650337) is a phase-3 clinical-stage small-molecule trace amine-associated receptor 1 agonist targeting HTR1A and TAAR1; indicated across 5 conditions including generalized anxiety disorder and major depressive disorder.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 2 (HTR1A, TAAR1)
- Indications: 5 conditions
- Clinical trials: 25
- Chemistry: 183.27 Da · C9H13NOS
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL4650337 |
| Name | Ulotaront |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 89532783 |
| ChEBI | CHEBI:228346 |
| Molecular formula | C9H13NOS |
| Molecular weight | 183.27 |
| InChIKey | ABDDQTDRAHXHOC-QMMMGPOBSA-N |
SMILES: CNC[C@H]1C2=C(CCO1)C=CS2
IUPAC name: 1-[(7S)-5,7-dihydro-4H-thieno[2,3-c]pyran-7-yl]-N-methylmethanamine
ChEBI definition: A member of the class of thienopyrans that is 4,7-dihydro-5H-thieno[2,3-c]pyran substituted by a (methylamino)methyl at position 7S. It is a trace amine-associated receptor 1 and serotonin 5-HT1A receptors agonist that has demonstrated efficacy in the treatment of patients with schizophrenia.
Pharmacological roles (ChEBI): trace amine-associated receptor 1 agonist, psychotropic drug, antidepressant, antipsychotic agent, serotonergic agonist.
Also known as: Sep-363856, SEP-363856, SEP-856, Ulotaront, ULOTARONT
Parent form; salt/anhydrous children: CHEMBL5314561
Patent coverage: 41 distinct patent families (118 SureChEMBL compound mentions), from 1 matched compound structure(s). 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 |
|---|---|---|---|---|---|
| HTR1A | 5-HT1A receptor | Agonist | 5.64 | 0% | P08908 |
| TAAR1 | TA1 receptor | Agonist | 6.85 | 0% | Q96RJ0 |
Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: 5-hydroxytryptamine receptor 1A, D(2) dopamine receptor, 5-hydroxytryptamine receptor 7, Trace amine-associated receptor 1.
Bioactivity
ChEMBL activities: 8 potent at pChembl ≥ 5 of 10 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| TAAR1 | 7.79 | EC50 | 16.3 | nM | CHEMBL_ACT_25895922 |
| TAAR1 | 7.68 | EC50 | 21.08 | nM | CHEMBL_ACT_25895947 |
| TAAR1 | 7.42 | EC50 | 38 | nM | CHEMBL_ACT_24366756 |
| TAAR1 | 6.85 | EC50 | 140 | nM | CHEMBL_ACT_25001816 |
| TAAR1 | 6.46 | EC50 | 349 | nM | CHEMBL_ACT_29182442 |
| HTR7 | 6.23 | EC50 | 590 | nM | CHEMBL_ACT_29182705 |
| HTR1A | 5.64 | EC50 | 2300 | nM | CHEMBL_ACT_25001818 |
| DRD2 | 5 | EC50 | 10000 | nM | CHEMBL_ACT_25001822 |
Target pathways
Aggregated over 2 target gene(s): HTR1A, TAAR1.
Top Reactome pathways
8 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Signal Transduction | 2 | HTR1A, TAAR1 |
| Signaling by GPCR | 2 | HTR1A, TAAR1 |
| Class A/1 (Rhodopsin-like receptors) | 2 | HTR1A, TAAR1 |
| Amine ligand-binding receptors | 2 | HTR1A, TAAR1 |
| GPCR ligand binding | 2 | HTR1A, TAAR1 |
| GPCR downstream signalling | 1 | TAAR1 |
| Serotonin receptors | 1 | HTR1A |
| G alpha (s) signalling events | 1 | TAAR1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| G protein-coupled receptor signaling pathway | 2 |
| signal transduction | 2 |
| adenylate cyclase-activating G protein-coupled receptor signaling pathway | 2 |
| behavioral fear response | 1 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 1 |
| adenylate cyclase-inhibiting serotonin receptor signaling pathway | 1 |
| serotonin receptor signaling pathway | 1 |
| gamma-aminobutyric acid signaling pathway | 1 |
| chemical synaptic transmission | 1 |
| positive regulation of cell population proliferation | 1 |
| regulation of serotonin secretion | 1 |
| regulation of vasoconstriction | 1 |
| adult behavior | 1 |
| exploration behavior | 1 |
| regulation of dopamine metabolic process | 1 |
Indications & clinical
Indications
5 indications (0 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 |
|---|---|---|---|
| generalized anxiety disorder | 2 | MONDO:0001942 | EFO:1001892 |
| major depressive disorder | 2 | MONDO:0002009 | MONDO:0002009 |
| Parkinson disease | 1 | MONDO:0005180 | MONDO:0005180 |
| narcolepsy | 1 | MONDO:0021107 | MONDO:0016158 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 25.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 11 |
| PHASE3 | 8 |
| PHASE2 | 4 |
| PHASE2/PHASE3 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06894212 | PHASE3 | RECRUITING | A Trial of the Efficacy and Safety of SEP-363856 in Acutely Psychotic Participants With Schizophrenia |
| NCT07225712 | PHASE3 | RECRUITING | A Long-term Administration Trial of SEP-363856 in Patients With Schizophrenia |
| NCT04072354 | PHASE3 | COMPLETED | A Clinical Trial to Study the Efficacy and Safety of an Investigational Drug in Acutely Psychotic People With Schizophrenia |
| NCT04092686 | PHASE3 | COMPLETED | A Clinical Trial That Will Study the Efficacy and Safety of an Investigational Drug in Acutely Psychotic People With Schizophrenia |
| NCT04109950 | PHASE3 | TERMINATED | A Clinical Study to Evaluate the Long-term Safety and Tolerability of an Investigational Drug in People With Schizophrenia |
| NCT04825860 | PHASE2/PHASE3 | TERMINATED | A Clinical Trial to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic People With Schizophrenia, Followed by an Open-label Extension Phase |
| NCT05359081 | PHASE3 | TERMINATED | A Clinical Trial to Evaluate the Long-term Safety and Tolerability of SEP-363856 in Patients With Schizophrenia in Japan |
| NCT05628103 | PHASE3 | COMPLETED | A Clinical Study That Will Evaluate How Well SEP-363856 Works and How Safe it is in People With Schizophrenia That Switch to SEP-363856 From Their Current Antipsychotic Medication |
| NCT05729373 | PHASE2/PHASE3 | COMPLETED | A Clinical Study That Will Measure How Well SEP-363856 Works and How Safe it is in Adults With Generalized Anxiety Disorder |
| NCT05741528 | PHASE3 | COMPLETED | An Extension Study to a Clinical Study That Will Continue to Evaluate the Effectiveness and Safety of SEP-363856 in People With Schizophrenia That Switch to SEP-363856 From Their From Their Current Antipsychotic Medication |
| NCT02969369 | PHASE2 | COMPLETED | A Study to Evaluate the Efficacy, Safety and Tolerability of SEP-363856 in Subjects With Parkinson’s Disease Psychosis |
| NCT02969382 | PHASE2 | COMPLETED | A Study to Evaluate the Efficacy and Safety of SEP-363856 in Acutely Psychotic Adults With Schizophrenia |
| NCT02970929 | PHASE2 | COMPLETED | An Extension Study of Safety and Tolerability of SEP-363856 in Adult Subjects With Schizophrenia |
| NCT05593029 | PHASE2 | COMPLETED | A Trial of the Safety and Efficacy of SEP-363856 in the Treatment of Adults With Major Depressive Disorder |
| NCT01940159 | PHASE1 | COMPLETED | A Study Assessing the Safety, Tolerability, and Pharmacokinetics of SEP-363856 in Male and Female Subjects With Schizophrenia |
| NCT01972711 | PHASE1 | COMPLETED | Study Assessing SEP-363856 in Male and Female Volunteers With High or Low Schizotype Characteristics |
| NCT01994473 | PHASE1 | COMPLETED | Study Assessing the Safety, Tolerability, and Pharmacokinetics of SEP-363856 in Male and Female Subjects With Schizophrenia |
| NCT03370640 | PHASE1 | COMPLETED | Study Assessing the Safety, Tolerability, and Pharmacokinetics of SEP-363856 in Japanese Male and Female Subjects With Schizophrenia in 2 Parts (Part 1 and 2). |
| NCT04038957 | PHASE1 | COMPLETED | A Clinical Study to Investigate the Effect of an Investigational Drug as an Added Medication to an Antipsychotic, in Adults With Schizophrenia, as Measured Positron Emission Tomography (PET) Imaging |
| NCT04325737 | PHASE1 | COMPLETED | Study Assessing the Safety, Tolerability, and Pharmacokinetics of SEP-363856 in Japanese Male and Female Subjects With Schizophrenia |
| NCT04865835 | PHASE1 | COMPLETED | A Clinical Trial Study to Determine the Effect of an Investigational Drug (SEP-363856) Has on the Way That the Drug Metformin Travels Through the Body in People With Schizophrenia. |
| NCT05402111 | PHASE1 | COMPLETED | A Clinical Study That Will Assess How Food Moves Through the Stomach and Effects Blood Glucose Levels in Subjects With Schizophrenia Taking SEP-363856 or and Prior Antipsychotic (PA) Standard |
| NCT05463770 | PHASE1 | COMPLETED | A Clinical Study That Will Assess the Effect of SEP-363856 and Prior Antipsychotic (PA) Standard of Care on Glucose and Regulation of Insulin in Patients With Schizophrenia |
| NCT05542264 | PHASE1 | COMPLETED | A Clinical Study That Will Assess the Effect of SEP-363856 or Prior Antipsychotic (PA) Standard of Care on Body-weight Associated Parameters in Subjects With Schizophrenia |
| NCT05848700 | PHASE1 | COMPLETED | A Clinical Study to Learn if SEP-363856 Has Physical Dependence in Adults With Schizophrenia |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 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.
420 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| DOPAMINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1A, TAAR1 |
| PYRIMETHAMINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1A, TAAR1 |
| ANTAZOLINE | ChEMBL | Phase 4 (approved) | HTR1A, TAAR1 |
| FENOLDOPAM | ChEMBL | Phase 4 (approved) | HTR1A, TAAR1 |
| GUANABENZ | ChEMBL | Phase 4 (approved) | HTR1A, TAAR1 |
| NAPHAZOLINE | ChEMBL | Phase 4 (approved) | HTR1A, TAAR1 |
| TETRAHYDROZOLINE | ChEMBL | Phase 4 (approved) | HTR1A, TAAR1 |
| SEROTONIN | ChEMBL + PubChem | Phase 3 (approved) | HTR1A, TAAR1 |
| TYRAMINE | ChEMBL | Phase 3 | HTR1A, TAAR1 |
| DEXTROAMPHETAMINE | ChEMBL + PubChem | Phase 4 (approved) | TAAR1 |
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | HTR1A |
| METHAMPHETAMINE | ChEMBL + PubChem | Phase 4 (approved) | TAAR1 |
| PHENTERMINE | ChEMBL + PubChem | Phase 4 (approved) | TAAR1 |
| TOLAZOLINE | ChEMBL + PubChem | Phase 4 (approved) | TAAR1 |
| ACEMETACIN | ChEMBL | Phase 4 (approved) | HTR1A |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | HTR1A |
| ACETYLCHOLINE | ChEMBL | Phase 4 (approved) | HTR1A |
| ALMOTRIPTAN | ChEMBL | Phase 4 (approved) | HTR1A |
| AMILORIDE | ChEMBL | Phase 4 (approved) | HTR1A |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | HTR1A |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | HTR1A |
| AMODIAQUINE | ChEMBL | Phase 4 (approved) | HTR1A |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | HTR1A |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | HTR1A |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | HTR1A |
| ARTICAINE | ChEMBL | Phase 4 (approved) | HTR1A |
| ASENAPINE | ChEMBL | Phase 4 (approved) | HTR1A |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | HTR1A |
| AZATADINE | ChEMBL | Phase 4 (approved) | HTR1A |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | HTR1A |
| BEDAQUILINE | ChEMBL | Phase 4 (approved) | HTR1A |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | HTR1A |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | HTR1A |
| BENZIODARONE | ChEMBL | Phase 4 (approved) | HTR1A |
| BENZYDAMINE | ChEMBL | Phase 4 (approved) | HTR1A |
| BEXAROTENE | ChEMBL | Phase 4 (approved) | HTR1A |
| BITHIONOL | ChEMBL | Phase 4 (approved) | HTR1A |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | HTR1A |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | HTR1A |
| BRIMONIDINE | ChEMBL | Phase 4 (approved) | HTR1A |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | HTR1A |
| BROMODIPHENHYDRAMINE | ChEMBL | Phase 4 (approved) | HTR1A |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | HTR1A |
| BUFLOMEDIL | ChEMBL | Phase 4 (approved) | HTR1A |
| BUSPIRONE | ChEMBL | Phase 4 (approved) | HTR1A |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | HTR1A |
| CALCIPOTRIENE | ChEMBL | Phase 4 (approved) | HTR1A |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | HTR1A |
| CANNABIDIOL | ChEMBL | Phase 4 (approved) | HTR1A |
| CARBAMOYLCHOLINE | ChEMBL | Phase 4 (approved) | HTR1A |
| CARBENOXOLONE | ChEMBL | Phase 4 (approved) | HTR1A |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | HTR1A |
| CARTEOLOL | ChEMBL | Phase 4 (approved) | HTR1A |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | HTR1A |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | HTR1A |
| CHLOROXINE | ChEMBL | Phase 4 (approved) | HTR1A |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | HTR1A |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | HTR1A |
| CINACALCET | ChEMBL | Phase 4 (approved) | HTR1A |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | HTR1A |
Related Atlas pages
- Genes: HTR1A, TAAR1
- Drugs: Dopamine, Pyrimethamine, Antazoline, Fenoldopam, Guanabenz, Naphazoline, Tetrahydrozoline, Serotonin, Tyramine, Dextroamphetamine, Dihydroergotamine, Methamphetamine, Phentermine, Tolazoline, Acemetacin, Acetophenazine, Acetylcholine, Almotriptan, Amiloride, Amitriptyline, Amlodipine, Amodiaquine, Amoxapine, Apomorphine, Aripiprazole, Articaine, Asenapine, Astemizole, Azatadine, Bazedoxifene, Bedaquiline, Benfluorex, Benperidol, Benziodarone, Benzydamine, Bexarotene, Bithionol, Bosutinib, Brexpiprazole, Brimonidine, Bromocriptine, Bromodiphenhydramine, Bromperidol, Buflomedil, Buspirone, Cabergoline, Calcipotriene, Candesartan Cilexetil, Cannabidiol, Carbamoylcholine, Carbenoxolone, Cariprazine, Carteolol, Carvedilol, Chlorhexidine, Chloroxine, Chlorpromazine, Chlorprothixene, Cinacalcet, Cinnarizine