Dextrothyroxine
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Also known as D-thyroxineSID11112110D-T4
Summary
Dextrothyroxine (CHEMBL559) is an approved small molecule (ATC C10AX01) targeting THRA and THRB; indicated across 2 conditions including cardiovascular disorder and down syndrome.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: C10AX01
- Targets: 2 (THRA, THRB)
- Indications: 2 conditions
- Chemistry: 776.87 Da · C15H11I4NO4
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL559 |
| Name | Dextrothyroxine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 8730 |
| ChEBI | CHEBI:30659 |
| ATC | C10AX01 |
| Molecular formula | C15H11I4NO4 |
| Molecular weight | 776.87 |
| InChIKey | XUIIKFGFIJCVMT-GFCCVEGCSA-N |
SMILES: C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)C[C@H](C(=O)O)N
IUPAC name: (2R)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
ChEBI definition: The D-enantiomer of thyroxine.
Also known as: D-thyroxine, Dextrothyroxine, SID11112110, D-T4, DEXTROTHYROXINE, dextrothyroxine
Parent form; salt/anhydrous children: CHEMBL1200777, CHEMBL3545058
Patent coverage: 1,138 distinct patent families (3,634 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 |
|---|---|---|---|---|---|
| THRA | Thyroid hormone receptor-α | Agonist | 1.7% | P10827 | |
| THRB | Thyroid hormone receptor-β | Agonist | 0% | P10828 |
Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: Fructose-bisphosphate aldolase, Prelamin-A/C, 5-hydroxytryptamine receptor 2B, Glutamate NMDA receptor, Thyroid hormone receptor beta, Glucocorticoid receptor, Thromboxane A2 receptor, Solute carrier organic anion transporter family member 1C1, Menin/Histone-lysine N-methyltransferase MLL, 5-hydroxytryptamine receptor 1A.
Bioactivity
ChEMBL activities: 12 potent at pChembl ≥ 5 of 22 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| THRB | 8.25 | Potency | 5.6 | nM | CHEMBL_ACT_4015915 |
| P18113 | 7.46 | IC50 | 35 | nM | CHEMBL_ACT_332005 |
| LMNA | 7.05 | Potency | 89.1 | nM | CHEMBL_ACT_3651302 |
| PDE4D | 6.58 | AC50 | 260 | nM | CHEMBL_ACT_25185305 |
| Q9ERB5 | 6.57 | Ki | 270 | nM | CHEMBL_ACT_11002271 |
| P35439 | 6.48 | IC50 | 330 | nM | CHEMBL_ACT_843353 |
| P18113 | 5.6 | IC50 | 2500 | nM | CHEMBL_ACT_332006 |
| NTSR1 | 5.32 | AC50 | 4800 | nM | CHEMBL_ACT_25189981 |
| CYP2C9 | 5.2 | Potency | 6310 | nM | CHEMBL_ACT_5069230 |
| CYP2C9 | 5.2 | AC50 | 6310 | nM | CHEMBL_ACT_6001614 |
| TTR | 5.14 | IC50 | 7170 | nM | CHEMBL_ACT_1998894 |
| HTR1A | 5.09 | AC50 | 8200 | nM | CHEMBL_ACT_25216003 |
Target pathways
Aggregated over 2 target gene(s): THRA, THRB.
Top Reactome pathways
9 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Generic Transcription Pathway | 2 | THRA, THRB |
| Nuclear Receptor transcription pathway | 2 | THRA, THRB |
| SUMOylation of intracellular receptors | 2 | THRA, THRB |
| RNA Polymerase II Transcription | 2 | THRA, THRB |
| Gene expression (Transcription) | 2 | THRA, THRB |
| SUMOylation | 1 | THRB |
| SUMO E3 ligases SUMOylate target proteins | 1 | THRB |
| Metabolism of proteins | 1 | THRB |
| Post-translational protein modification | 1 | THRB |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| negative regulation of transcription by RNA polymerase II | 2 |
| thyroid hormone receptor signaling pathway | 2 |
| positive regulation of thyroid hormone receptor signaling pathway | 2 |
| regulation of transcription by RNA polymerase II | 2 |
| regulation of heart contraction | 2 |
| female courtship behavior | 2 |
| cell differentiation | 2 |
| mRNA transcription by RNA polymerase II | 2 |
| negative regulation of DNA-templated transcription | 2 |
| positive regulation of transcription by RNA polymerase II | 2 |
| retinoic acid receptor signaling pathway | 2 |
| type I pneumocyte differentiation | 2 |
| regulation of DNA-templated transcription | 2 |
| animal organ morphogenesis | 2 |
| intracellular receptor signaling pathway | 2 |
Indications & clinical
Indications
2 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 |
|---|---|---|---|
| cardiovascular disorder | 4 | MONDO:0004995 | EFO:0000319 |
| Down syndrome | 3 | MONDO:0008608 | EFO:0001064 |
Clinical trials
Total trials: 0.
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.
112 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| AMIODARONE | ChEMBL + PubChem | Phase 4 (approved) | THRA, THRB |
| LIOTHYRONINE | ChEMBL + PubChem | Phase 4 (approved) | THRA, THRB |
| RESMETIROM | ChEMBL + PubChem | Phase 4 (approved) | THRA, THRB |
| LEVOTHYROXINE | ChEMBL | Phase 4 (approved) | THRA, THRB |
| ROXADUSTAT | ChEMBL | Phase 4 (approved) | THRA, THRB |
| EPROTIROME | ChEMBL | Phase 3 | THRA, THRB |
| TIRATRICOL | ChEMBL | Phase 3 | THRA, THRB |
| AXITIROME | ChEMBL | Phase 2 | THRA, THRB |
| DETROTHYRONINE | ChEMBL | Phase 2 | THRA, THRB |
| MB07811 | ChEMBL | Phase 2 | THRA, THRB |
| SOBETIROME | ChEMBL | Phase 2 | THRA, THRB |
| THYROPROPIC ACID | ChEMBL | Phase 2 | THRA, THRB |
| ACETAZOLAMIDE | ChEMBL | Phase 4 (approved) | THRB |
| ACETOHEXAMIDE | ChEMBL | Phase 4 (approved) | THRB |
| ACETYLCYSTEINE | ChEMBL | Phase 4 (approved) | THRB |
| ALTRETAMINE | ChEMBL | Phase 4 (approved) | THRB |
| AMANTADINE | ChEMBL | Phase 4 (approved) | THRB |
| AMILORIDE | ChEMBL | Phase 4 (approved) | THRB |
| AMINOCAPROIC ACID | ChEMBL | Phase 4 (approved) | THRB |
| AMINOPYRINE | ChEMBL | Phase 4 (approved) | THRB |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | THRB |
| ATORVASTATIN | ChEMBL | Phase 4 (approved) | THRB |
| AZARIBINE | ChEMBL | Phase 4 (approved) | THRB |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | THRB |
| BISOPROLOL | ChEMBL | Phase 4 (approved) | THRB |
| BITHIONOL | ChEMBL | Phase 4 (approved) | THRB |
| CARBETAPENTANE | ChEMBL | Phase 4 (approved) | THRB |
| CHLORMADINONE | ChEMBL | Phase 4 (approved) | THRB |
| CHLORMEZANONE | ChEMBL | Phase 4 (approved) | THRB |
| CHLORPROPAMIDE | ChEMBL | Phase 4 (approved) | THRB |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | THRB |
| CYCLOTHIAZIDE | ChEMBL | Phase 4 (approved) | THRB |
| CYTARABINE | ChEMBL | Phase 4 (approved) | THRB |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | THRB |
| DEBRISOQUIN | ChEMBL | Phase 4 (approved) | THRB |
| DIAZOXIDE | ChEMBL | Phase 4 (approved) | THRB |
| DILTIAZEM | ChEMBL | Phase 4 (approved) | THRB |
| DIPYRIDAMOLE | ChEMBL | Phase 4 (approved) | THRB |
| DISOPYRAMIDE | ChEMBL | Phase 4 (approved) | THRB |
| DITHIAZANINE IODIDE | ChEMBL | Phase 4 (approved) | THRB |
| DOXORUBICIN | ChEMBL | Phase 4 (approved) | THRB |
| DYCLONINE | ChEMBL | Phase 4 (approved) | THRB |
| GENTIAN VIOLET | ChEMBL | Phase 4 (approved) | THRB |
| HEXACHLOROPHENE | ChEMBL | Phase 4 (approved) | THRB |
| HYDROCHLOROTHIAZIDE | ChEMBL | Phase 4 (approved) | THRB |
| IDARUBICIN | ChEMBL | Phase 4 (approved) | THRB |
| INAMRINONE | ChEMBL | Phase 4 (approved) | THRB |
| INDIGOTINDISULFONATE | ChEMBL | Phase 4 (approved) | THRB |
| ISOSORBIDE | ChEMBL | Phase 4 (approved) | THRB |
| ISOTRETINOIN | ChEMBL | Phase 4 (approved) | THRB |
| LEFLUNOMIDE | ChEMBL | Phase 4 (approved) | THRB |
| MECLOFENAMATE | ChEMBL | Phase 4 (approved) | THRB |
| MESALAMINE | ChEMBL | Phase 4 (approved) | THRB |
| METHACYCLINE | ChEMBL | Phase 4 (approved) | THRB |
| METHYLENE BLUE | ChEMBL | Phase 4 (approved) | THRB |
| METHYLENE BLUE CATION | ChEMBL | Phase 4 (approved) | THRB |
| METHYSERGIDE | ChEMBL | Phase 4 (approved) | THRB |
| METRONIDAZOLE | ChEMBL | Phase 4 (approved) | THRB |
| MOLSIDOMINE | ChEMBL | Phase 4 (approved) | THRB |
| OXYTETRACYCLINE | ChEMBL | Phase 4 (approved) | THRB |
Related Atlas pages
- Genes: THRA, THRB
- Diseases: cardiovascular disorder, Down syndrome
- Drugs: Amiodarone, Liothyronine, Resmetirom, Levothyroxine, Roxadustat, Eprotirome, Tiratricol, Acetazolamide, Acetohexamide, Acetylcysteine, Altretamine, Amantadine, Amiloride, Aminocaproic Acid, Aminopyrine, Amoxapine, Atorvastatin, Azaribine, Benzbromarone, Bisoprolol, Bithionol, Carbetapentane, Chlormadinone, Chlormezanone, Chlorpropamide, Clomipramine, Cyclothiazide, Cytarabine, Daunorubicin, Debrisoquin, Diazoxide, Diltiazem, Dipyridamole, Disopyramide, Doxorubicin, Dyclonine, Hexachlorophene, Hydrochlorothiazide, Idarubicin, Inamrinone, Isosorbide, Isotretinoin, Leflunomide, Meclofenamate, Mesalamine, Methacycline, Methylene Blue, Methysergide, Metronidazole, Molsidomine, Oxytetracycline