Thiothixene
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Also known as (z)-thiothixeneCis-thiothixeneNavaneNSC-108165OrbinamonP-4657 BP-4657BThiothixene cis-isomerTiotixeneTiotixenoSID11532885SID50111253SID144203829ThiothixeneÊThiothixeneÂC0165000
Summary
Thiothixene (CHEMBL1201) is an approved small molecule (ATC N05AF04) targeting HRH1 and HTR2A; indicated across 2 conditions including psychotic disorder.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N05AF04
- Targets: 2 (HRH1, HTR2A)
- Indications: 2 conditions
- Clinical trials: 1
- Chemistry: 443.6 Da · C23H29N3O2S2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1201 |
| Name | Thiothixene |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 941651 |
| ATC | N05AF04 |
| Molecular formula | C23H29N3O2S2 |
| Molecular weight | 443.6 |
| InChIKey | GFBKORZTTCHDGY-UWVJOHFNSA-N |
SMILES: CN1CCN(CC1)CC/C=C\2/C3=CC=CC=C3SC4=C2C=C(C=C4)S(=O)(=O)N(C)C
IUPAC name: (9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]thioxanthene-2-sulfonamide
Also known as: (z)-thiothixene, Cis-thiothixene, Navane, NSC-108165, Orbinamon, P-4657 B, P-4657B, Thiothixene, Thiothixene cis-isomer, Tiotixene, Tiotixeno, SID11532885
Parent form; salt/anhydrous children: CHEMBL1200902, CHEMBL3989824
Patent coverage: 3,413 distinct patent families (13,101 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 12,974 (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 |
|---|---|---|---|---|---|
| HRH1 | H1 receptor | Antagonist | 8.4 | 0% | P35367 |
| HTR2A | 5-HT2A receptor | Antagonist | 7.3 | 0% | P28223 |
Broader ChEMBL bioactivity targets: 30 (assay-derived). Sample: Lysine-specific demethylase 4E, Histone-lysine N-methyltransferase 2A, Vasopressin V2 receptor, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, 5-hydroxytryptamine receptor 3A, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, D(1A) dopamine receptor.
Bioactivity
ChEMBL activities: 29 potent at pChembl ≥ 5 of 38 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| DRD2 | 8.57 | AC50 | 2.7 | nM | CHEMBL_ACT_25139838 |
| DRD3 | 7.86 | AC50 | 13.9 | nM | CHEMBL_ACT_25193041 |
| DRD1 | 7.72 | AC50 | 19 | nM | CHEMBL_ACT_25115839 |
| ADRA1A | 7.61 | AC50 | 24.4 | nM | CHEMBL_ACT_25137642 |
| HRH1 | 7.44 | AC50 | 36 | nM | CHEMBL_ACT_25212013 |
| ADRA1A | 7.21 | AC50 | 62.4 | nM | CHEMBL_ACT_25138333 |
| DRD1 | 7.11 | AC50 | 77.4 | nM | CHEMBL_ACT_25114614 |
| ADRA2B | 7.11 | AC50 | 78 | nM | CHEMBL_ACT_25143215 |
| HTR2A | 6.96 | AC50 | 110.6 | nM | CHEMBL_ACT_25173448 |
| HRH2 | 6.84 | AC50 | 144.9 | nM | CHEMBL_ACT_25114331 |
| HTR7 | 6.59 | AC50 | 254.4 | nM | CHEMBL_ACT_25119050 |
| ADRA1A | 6.51 | AC50 | 310 | nM | CHEMBL_ACT_25217730 |
| HTR6 | 6.34 | AC50 | 455.4 | nM | CHEMBL_ACT_25118902 |
| HTR1A | 6.31 | AC50 | 494.5 | nM | CHEMBL_ACT_25164356 |
| ADRA2A | 6.12 | AC50 | 754.8 | nM | CHEMBL_ACT_25155816 |
| DRD4 | 6.11 | AC50 | 779.6 | nM | CHEMBL_ACT_25127291 |
| HTR2B | 6.07 | AC50 | 857.3 | nM | CHEMBL_ACT_25163986 |
| DRD1 | 6.01 | AC50 | 980 | nM | CHEMBL_ACT_25181212 |
| HTR2A | 5.89 | AC50 | 1300 | nM | CHEMBL_ACT_25224719 |
| ADRA2C | 5.85 | AC50 | 1400 | nM | CHEMBL_ACT_25147378 |
| HTR1A | 5.85 | AC50 | 1400 | nM | CHEMBL_ACT_25215660 |
| HTR3A | 5.8 | AC50 | 1600 | nM | CHEMBL_ACT_25148638 |
| KCNH2 | 5.79 | AC50 | 1630 | nM | CHEMBL_ACT_25117124 |
| HTR2C | 5.55 | AC50 | 2800 | nM | CHEMBL_ACT_25131323 |
| TACR1 | 5.42 | AC50 | 3838 | nM | CHEMBL_ACT_25128662 |
| PDE4D | 5.39 | AC50 | 4100 | nM | CHEMBL_ACT_25184827 |
| HTR2B | 5.31 | AC50 | 4900 | nM | CHEMBL_ACT_25227060 |
| ADRA2A | 5.23 | AC50 | 5900 | nM | CHEMBL_ACT_25219428 |
| SLC6A3 | 5.2 | AC50 | 6260 | nM | CHEMBL_ACT_25123464 |
Target pathways
Aggregated over 2 target gene(s): HRH1, HTR2A.
Top Reactome pathways
9 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| G alpha (q) signalling events | 2 | HRH1, HTR2A |
| Signal Transduction | 1 | HTR2A |
| Signaling by GPCR | 1 | HTR2A |
| Class A/1 (Rhodopsin-like receptors) | 1 | HTR2A |
| Amine ligand-binding receptors | 1 | HTR2A |
| GPCR downstream signalling | 1 | HTR2A |
| Histamine receptors | 1 | HRH1 |
| Serotonin receptors | 1 | HTR2A |
| GPCR ligand binding | 1 | HTR2A |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| G protein-coupled receptor signaling pathway | 2 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 2 |
| chemical synaptic transmission | 2 |
| memory | 2 |
| positive regulation of vasoconstriction | 2 |
| signal transduction | 2 |
| phospholipase C-activating serotonin receptor signaling pathway | 2 |
| inflammatory response | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| visual learning | 1 |
| regulation of vascular permeability | 1 |
| regulation of synaptic plasticity | 1 |
| cellular response to histamine | 1 |
| temperature homeostasis | 1 |
| positive regulation of cytokine production involved in immune response | 1 |
Indications & clinical
Indications
2 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 |
|---|---|---|---|
| psychotic disorder | 4 | MONDO:0005485 | EFO:0005407 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 1.
Phase distribution
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT02600741 | Not specified | COMPLETED | Family Intervention in Recent Onset Schizophrenia Treatment (FIRST) |
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.
481 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| Almotriptan | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| Crizotinib | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| DESLORATADINE | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| Erythromycin | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| Fidaxomicin | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| Olodaterol | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| PALIPERIDONE | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| PRAMIPEXOLE | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| Propoxyphene | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| Tamsulosin | ChEMBL + PubChem | Phase 4 (approved) | HRH1, HTR2A |
| ABEMACICLIB | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| AMIODARONE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| AMISULPRIDE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| ASENAPINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| AZATADINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| AZELASTINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BUSPIRONE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| BUTRIPTYLINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CAPTOPRIL | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CETIRIZINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CHLORPHENTERMINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CINACALCET | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CISAPRIDE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CITALOPRAM | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CLOZAPINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CYCLIZINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CYCLOBENZAPRINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| DESIPRAMINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| DEXBROMPHENIRAMINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| DEXCHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| DIBENZEPIN | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| DICYCLOMINE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| DIETHYLPROPION | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| DIMENHYDRINATE | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
| DIPHEMANIL | ChEMBL | Phase 4 (approved) | HRH1, HTR2A |
Related Atlas pages
- Genes: HRH1, HTR2A
- Diseases: psychotic disorder
- Drugs: Almotriptan, Crizotinib, Desloratadine, Dihydroergotamine, Erythromycin, Fidaxomicin, Olodaterol, Paliperidone, Pramipexole, Propoxyphene, Tamsulosin, Abemaciclib, Acetophenazine, Amiodarone, Amisulpride, Amitriptyline, Amoxapine, Apomorphine, Aripiprazole, Asenapine, Astemizole, Atomoxetine, Azatadine, Azelastine, Benfluorex, Benperidol, Benzbromarone, Benztropine, Bepridil, Brexpiprazole, Bromperidol, Buspirone, Butriptyline, Cabergoline, Candesartan Cilexetil, Captopril, Cariprazine, Cetirizine, Chlorpheniramine, Chlorphentermine, Chlorpromazine, Cinacalcet, Cinnarizine, Cisapride, Citalopram, Clemastine, Clomipramine, Clotrimazole, Clozapine, Cyclizine, Cyclobenzaprine, Cyproheptadine, Desipramine, Dexbrompheniramine, Dibenzepin, Dicyclomine, Diethylpropion, Dimenhydrinate, Diphemanil