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Liothyronine

drug
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Also known as 3,5,3'-triiodothyronine, l-CyronineEuthroid-0.5Euthroid-1Euthroid-2Euthroid-3LiotironinaNSC-80203Rathyronine, (s)-Thyrolar-0.25Thyrolar-0.5Thyrolar-1Thyrolar-2Thyrolar-3Thyrolar-53,5,3'-triiodo-L-thyronine3,5,3'-triidodo-L-thyronineSID11532858SID4253003

Summary

Liothyronine (CHEMBL1544) is an approved small-molecule thyroid hormone targeting THRA and THRB; indicated across 12 conditions including hypothyroidism and depressive disorder.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • Targets: 2 (THRA, THRB)
  • Indications: 12 conditions
  • Clinical trials: 34
  • Chemistry: 650.97 Da · C15H12I3NO4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1544
NameLiothyronine
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID5920
ChEBICHEBI:18258
Molecular formulaC15H12I3NO4
Molecular weight650.97
InChIKeyAUYYCJSJGJYCDS-LBPRGKRZSA-N

SMILES: C1=CC(=C(C=C1OC2=C(C=C(C=C2I)C[C@@H](C(=O)O)N)I)I)O

IUPAC name: (2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid

ChEBI definition: An iodothyronine compound having iodo substituents at the 3-, 3’- and 5-positions. Although some is produced in the thyroid, most of the 3,3’,5-triiodo-L-thyronine in the body is generated by mono-deiodination of L-thyroxine in the peripheral tissues. Its metabolic activity is about 3 to 5 times that of L-thyroxine. The sodium salt is used in the treatment of hypothyroidism.

Pharmacological roles (ChEBI): thyroid hormone.

Other ChEBI roles (chemical / environmental): human metabolite, mouse metabolite.

Also known as: 3,5,3’-triiodothyronine, l-, Cyronine, Euthroid-0.5, Euthroid-1, Euthroid-2, Euthroid-3, Liothyronine, Liotironina, NSC-80203, Rathyronine, (s)-, Thyrolar-0.25, Thyrolar-0.5

Parent form; salt/anhydrous children: CHEMBL1201119, CHEMBL1356342, CHEMBL2106622, CHEMBL2107398

Patent coverage: 7,735 distinct patent families (23,700 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 23,683 (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).

GeneTargetActionpAffinityCancer dependencyUniProt
THRAThyroid hormone receptor-αAgonist101.7%P10827
THRBThyroid hormone receptor-βAgonist10.10%P10828

Broader ChEMBL bioactivity targets: 16 (assay-derived). Sample: Prelamin-A/C, Solute carrier organic anion transporter family member 1A4, Thyroid hormone receptor alpha, GABA-A receptor; anion channel, Thyroid hormone receptor beta, Prothrombin, Solute carrier organic anion transporter family member 1C1, Menin/Histone-lysine N-methyltransferase MLL, GABA-A receptor; anion channel, Adenosine receptor A1.

Bioactivity

ChEMBL activities: 69 potent at pChembl ≥ 5 of 76 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
THRA10.24Kd0.06nMCHEMBL_ACT_2132728
THRA10.22Kd0.06nMCHEMBL_ACT_1197610
THRB10.1Ki0.08nMCHEMBL_ACT_1073950
THRB10.09Kd0.08nMCHEMBL_ACT_2132729
THRB10.06Kd0.09nMCHEMBL_ACT_1197611
THRB10Kd0.1nMCHEMBL_ACT_152718
THRA10Kd0.1nMCHEMBL_ACT_152719
THRB9.85Kd0.14nMCHEMBL_ACT_746450
THRA9.77Kd0.17nMCHEMBL_ACT_746449
THRA9.66Ki0.22nMCHEMBL_ACT_2187208
THRA9.62IC500.24nMCHEMBL_ACT_1604622
THRA9.62IC500.24nMCHEMBL_ACT_1969888
THRB9.59IC500.26nMCHEMBL_ACT_1604623
THRB9.59IC500.26nMCHEMBL_ACT_1969903
THRB9.59IC500.26nMCHEMBL_ACT_1972810
THRA9.48Ki0.33nMCHEMBL_ACT_2397548
THRA9.39EC500.41nMCHEMBL_ACT_15068917
THRA9.3EC500.5nMCHEMBL_ACT_20712949
THRB9.26Ki0.55nMCHEMBL_ACT_2187210
THRB9.17Ki0.68nMCHEMBL_ACT_2397575
THRA9.15EC500.7nMCHEMBL_ACT_25062802
THRA9EC501.01nMCHEMBL_ACT_27844262
THRB8.96EC501.1nMCHEMBL_ACT_25062822
F28.92EC501.2nMCHEMBL_ACT_20712946
F28.92EC501.2nMCHEMBL_ACT_20712950
THRB8.83EC501.49nMCHEMBL_ACT_27844265
P181138.74IC501.8nMCHEMBL_ACT_319278
THRB8.7EC502nMCHEMBL_ACT_1073952
THRA8.7EC502nMCHEMBL_ACT_1073953
THRB8.7EC502nMCHEMBL_ACT_13952550

Target pathways

Aggregated over 2 target gene(s): THRA, THRB.

Top Reactome pathways

9 total, by targets touching each:

PathwayTargetsGenes
Generic Transcription Pathway2THRA, THRB
Nuclear Receptor transcription pathway2THRA, THRB
SUMOylation of intracellular receptors2THRA, THRB
RNA Polymerase II Transcription2THRA, THRB
Gene expression (Transcription)2THRA, THRB
SUMOylation1THRB
SUMO E3 ligases SUMOylate target proteins1THRB
Metabolism of proteins1THRB
Post-translational protein modification1THRB

Dominant GO biological processes

GO termTargets
negative regulation of transcription by RNA polymerase II2
thyroid hormone receptor signaling pathway2
positive regulation of thyroid hormone receptor signaling pathway2
regulation of transcription by RNA polymerase II2
regulation of heart contraction2
female courtship behavior2
cell differentiation2
mRNA transcription by RNA polymerase II2
negative regulation of DNA-templated transcription2
positive regulation of transcription by RNA polymerase II2
retinoic acid receptor signaling pathway2
type I pneumocyte differentiation2
regulation of DNA-templated transcription2
animal organ morphogenesis2
intracellular receptor signaling pathway2

Indications & clinical

Indications

12 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).

IndicationTrial phaseMONDOEFO
hypothyroidism3MONDO:0005420EFO:0004705
depressive disorder3MONDO:0002050MONDO:0002050
bipolar disorder3MONDO:0004985MONDO:0004985
major depressive disorder3MONDO:0002009EFO:0003761
breast neoplasm2MONDO:0021100MONDO:0007254
toxic shock syndrome2MONDO:0001881EFO:0006834
euthyroid sick syndrome2MONDO:0006755EFO:1000931
atrial fibrillation1MONDO:0004981EFO:0000275
chronic progressive multiple sclerosis1MONDO:0005284EFO:0003840
relapsing-remitting multiple sclerosis1MONDO:0005314EFO:0003929
heart failure1MONDO:0005252EFO:0003144
gliosarcoma0MONDO:0016681EFO:1001465

Clinical trials

Total trials: 34.

Phase distribution

PhaseTrials
PHASE210
Not specified7
PHASE44
PHASE34
PHASE1/PHASE24
PHASE13
PHASE2/PHASE31
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00208702PHASE4COMPLETEDThyroid Medication and Antidepressants for Treating Major Depression
NCT00296686PHASE4TERMINATEDSequential Tranylcypromine (TC), TC + Dextroamphetamine and TC + Triiodothyronine for Refractory Depression
NCT00360074PHASE4COMPLETEDPhase 4 Study in Secondary Hypothyroidism: Body Weight Adapted Thyroxin Treatment and Triiodothyronine Supplementation
NCT00531713PHASE4COMPLETEDEffect of T4-T3 Combination Therapy Versus T4 Monotherapy in Patients With Hypothyroidism
NCT00027417PHASE3COMPLETEDStudy of Triostat in Infants During Heart Surgery
NCT00158990PHASE3COMPLETEDTriiodothyronine (T3) Supplementation in the Treatment of Bipolar and Unipolar Depression.
NCT00790738PHASE3COMPLETEDLiothyronine (T3) for Bipolar Depression
NCT02521168PHASE3COMPLETEDOral Triiodothyronine for Children Undergoing Cardiopulmonary Bypass in Indonesia
NCT03053115PHASE2/PHASE3COMPLETEDCombined Replacement Therapy With Levothyroxine and Liothyronine in Thyroidectomized Patients
NCT04115514PHASE2ACTIVE_NOT_RECRUITINGTreatment of ARDS With Instilled T3
NCT04743661PHASE2ACTIVE_NOT_RECRUITING131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma
NCT07346157PHASE1/PHASE2NOT_YET_RECRUITINGLiothyronine in Combination With BIT Regimen for Medulloblastoma With or Without Minimal Residual Disease
NCT07424183PHASE2NOT_YET_RECRUITINGT4/T3 Therapy in Hypothyroidism
NCT00106119PHASE2COMPLETEDThyroid and Glucose and Energy Metabolism
NCT01800617PHASE2COMPLETEDA Study of T3 Therapy in Patients With Hypothyroidism
NCT02457897PHASE2COMPLETEDThyroid Hormone to Induce Non-Insulin Mediated Glucose Disposal in People With Insulin Receptor Mutations
NCT03098433PHASE1/PHASE2COMPLETEDEffects of Liothyronine on Energy Expenditure and Cardiovascular Function
NCT03627611PHASE2COMPLETEDIdentification of Non-responders to Levothyroxine Therapy
NCT03787303PHASE2TERMINATEDStudy of Euthyroid Hypothyroxinemia in Metastatic Breast Carcinoma
NCT04111536PHASE1/PHASE2COMPLETEDDeveloping Oral LT3 Therapy for Heart Failure - HFpEF
NCT04112316PHASE1/PHASE2COMPLETEDDeveloping Oral LT3 Therapy for Heart Failure - HFrEF
NCT04782856PHASE2COMPLETEDEnergy Metabolism in Thyroidectomized Patients
NCT05270798PHASE2COMPLETEDThyroid Hormone Supplementation in Patients With Septic Shock
NCT00289367PHASE1COMPLETEDStudy of T3 on the Incidence of Atrial Fibrillation in Patients Undergoing Cardiac Surgery
NCT01581463PHASE1COMPLETEDA Study of Sustained-Release Liothyronine Sodium (T3) in Healthy Subjects
NCT02506751PHASE1COMPLETEDOpen-label Study of Liothyronine in MS
NCT05017610EARLY_PHASE1WITHDRAWNInducing a Hypothyroxinemic State in Patients With Recurrent Glioblastoma or Gliosarcoma
NCT07568574Not specifiedENROLLING_BY_INVITATIONImpact of Medically Supervised Performance-Enhancing Substances (PES) on Elite Athletes
NCT00223158Not specifiedCOMPLETEDEvaluation Study of L-T3 Utility in the Follow-up of Patients With Thyroid Cancer
NCT00421369Not specifiedCOMPLETEDAugmentation of the Antidepressant Action of Sertraline With Triiodothyronine (T3)and Reboxetine: Clinical Efficacy, Adverse Effects and Predictors of Response.
NCT00488644Not specifiedTERMINATEDCombined Levothyroxine/Liothyronine Supplementation in Hypothyroid Patients With Brain Tumors
NCT00715572Not specifiedCOMPLETEDCombined Therapy With L-Thyroxine and L-Triiodothyronine Compared to L-Thyroxine Alone
NCT01481402Not specifiedCOMPLETEDLiothyronine and Heart Failure. The Long Term Effect of Liothyronine on Left Ventricular Ejection Fraction (LVEF)
NCT02399475Not specifiedCOMPLETEDMechanistic Study of Subclinical Hypothyroidism In the Elderly

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 3 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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:

MoleculeSourceStatusShared targets
AMIODARONEChEMBL + PubChemPhase 4 (approved)THRA, THRB
RESMETIROMChEMBL + PubChemPhase 4 (approved)THRA, THRB
LEVOTHYROXINEChEMBLPhase 4 (approved)THRA, THRB
ROXADUSTATChEMBLPhase 4 (approved)THRA, THRB
EPROTIROMEChEMBLPhase 3THRA, THRB
TIRATRICOLChEMBLPhase 3THRA, THRB
AXITIROMEChEMBLPhase 2THRA, THRB
DETROTHYRONINEChEMBLPhase 2THRA, THRB
MB07811ChEMBLPhase 2THRA, THRB
SOBETIROMEChEMBLPhase 2THRA, THRB
THYROPROPIC ACIDChEMBLPhase 2THRA, THRB
ACETAZOLAMIDEChEMBLPhase 4 (approved)THRB
ACETOHEXAMIDEChEMBLPhase 4 (approved)THRB
ACETYLCYSTEINEChEMBLPhase 4 (approved)THRB
ALTRETAMINEChEMBLPhase 4 (approved)THRB
AMANTADINEChEMBLPhase 4 (approved)THRB
AMILORIDEChEMBLPhase 4 (approved)THRB
AMINOCAPROIC ACIDChEMBLPhase 4 (approved)THRB
AMINOPYRINEChEMBLPhase 4 (approved)THRB
AMOXAPINEChEMBLPhase 4 (approved)THRB
ATORVASTATINChEMBLPhase 4 (approved)THRB
AZARIBINEChEMBLPhase 4 (approved)THRB
BENZBROMARONEChEMBLPhase 4 (approved)THRB
BISOPROLOLChEMBLPhase 4 (approved)THRB
BITHIONOLChEMBLPhase 4 (approved)THRB
CARBETAPENTANEChEMBLPhase 4 (approved)THRB
CHLORMADINONEChEMBLPhase 4 (approved)THRB
CHLORMEZANONEChEMBLPhase 4 (approved)THRB
CHLORPROPAMIDEChEMBLPhase 4 (approved)THRB
CLOMIPRAMINEChEMBLPhase 4 (approved)THRB
CYCLOTHIAZIDEChEMBLPhase 4 (approved)THRB
CYTARABINEChEMBLPhase 4 (approved)THRB
DAUNORUBICINChEMBLPhase 4 (approved)THRB
DEBRISOQUINChEMBLPhase 4 (approved)THRB
DEXTROTHYROXINEChEMBLPhase 4 (approved)THRB
DIAZOXIDEChEMBLPhase 4 (approved)THRB
DILTIAZEMChEMBLPhase 4 (approved)THRB
DIPYRIDAMOLEChEMBLPhase 4 (approved)THRB
DISOPYRAMIDEChEMBLPhase 4 (approved)THRB
DITHIAZANINE IODIDEChEMBLPhase 4 (approved)THRB
DOXORUBICINChEMBLPhase 4 (approved)THRB
DYCLONINEChEMBLPhase 4 (approved)THRB
GENTIAN VIOLETChEMBLPhase 4 (approved)THRB
HEXACHLOROPHENEChEMBLPhase 4 (approved)THRB
HYDROCHLOROTHIAZIDEChEMBLPhase 4 (approved)THRB
IDARUBICINChEMBLPhase 4 (approved)THRB
INAMRINONEChEMBLPhase 4 (approved)THRB
INDIGOTINDISULFONATEChEMBLPhase 4 (approved)THRB
ISOSORBIDEChEMBLPhase 4 (approved)THRB
ISOTRETINOINChEMBLPhase 4 (approved)THRB
LEFLUNOMIDEChEMBLPhase 4 (approved)THRB
MECLOFENAMATEChEMBLPhase 4 (approved)THRB
MESALAMINEChEMBLPhase 4 (approved)THRB
METHACYCLINEChEMBLPhase 4 (approved)THRB
METHYLENE BLUEChEMBLPhase 4 (approved)THRB
METHYLENE BLUE CATIONChEMBLPhase 4 (approved)THRB
METHYSERGIDEChEMBLPhase 4 (approved)THRB
METRONIDAZOLEChEMBLPhase 4 (approved)THRB
MOLSIDOMINEChEMBLPhase 4 (approved)THRB
OXYTETRACYCLINEChEMBLPhase 4 (approved)THRB

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot