Tiratricol

Summary

Tiratricol (CHEMBL41632) is a phase-3 clinical-stage small-molecule thyroid hormone (ATC H03AA04) targeting THRA and THRB.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: H03AA04 (+1 more)
• Targets: 2 (THRA, THRB)
• Clinical trials: 5
• Chemistry: 621.93 Da · C14H9I3O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL41632
Name	Tiratricol
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	5803
ChEBI	CHEBI:40021
ATC	H03AA04, D11AX08
Molecular formula	C14H9I3O4
Molecular weight	621.93
InChIKey	UOWZUVNAGUAEQC-UHFFFAOYSA-N

SMILES: C1=CC(=C(C=C1OC2=C(C=C(C=C2I)CC(=O)O)I)I)O

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

ChEBI definition: A monocarboxylic acid that is (4-hydroxy-3,5-diiodophenyl)acetic acid in which the phenolic hydroxy group has been replaced by a 4-hydroxy-3-iodophenoxy group. It is a thyroid hormone analogue that has been used in the treatment of thyroid hormone resistance syndrome.

Pharmacological roles (ChEBI): thyroid hormone, antiviral agent, EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor, nutraceutical, anti-obesity agent.

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

Also known as: 3,5,3’-triiodothyroacetate, Levothyroxine sodium impurity, triiodothyroacetic acid, NSC-759294, Tiracana, Tiratricol, Triac, Triiodothyroacetic acid, SID11112109, SID855525, SID50100372, SID144213850

Patent coverage: 21,341 distinct patent families (46,632 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 46,627 (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
THRA	Thyroid hormone receptor-α	Agonist		1.7%	P10827
THRB	Thyroid hormone receptor-β	Agonist	10.7	0%	P10828

Broader ChEMBL bioactivity targets: 30 (assay-derived). Sample: Survival motor neuron protein, Prelamin-A/C, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], 5-hydroxytryptamine receptor 2B, Thyroid hormone receptor alpha, Alpha-2A adrenergic receptor, Androgen receptor, Thyroid hormone receptor beta, Retinoic acid receptor RXR-alpha, Solute carrier organic anion transporter family member 1C1.

Bioactivity

ChEMBL activities: 30 potent at pChembl ≥ 5 of 44 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
THRB	10.39	IC50	0.04	nM	CHEMBL_ACT_2056459
THRB	10.32	IC50	0.05	nM	CHEMBL_ACT_1038856
THRB	10.32	IC50	0.05	nM	CHEMBL_ACT_1972892
THRA	9.85	IC50	0.14	nM	CHEMBL_ACT_1038855
THRA	9.85	IC50	0.14	nM	CHEMBL_ACT_2056392
P18113	9.82	IC50	0.15	nM	CHEMBL_ACT_329461
THRA	8.7	EC50	2	nM	CHEMBL_ACT_26335914
THRB	8.4	EC50	4	nM	CHEMBL_ACT_26335915
PPARG	6.7	Kd	200	nM	CHEMBL_ACT_20712820
PPARG	6.43	EC50	370	nM	CHEMBL_ACT_20712810
RXRA	5.88	Kd	1320	nM	CHEMBL_ACT_20712833
Q9ERB5	5.67	Ki	2150	nM	CHEMBL_ACT_11002742
GABRA1	5.64	AC50	2300	nM	CHEMBL_ACT_25234015
PDE4D	5.53	AC50	2973	nM	CHEMBL_ACT_25185092
ADRA1A	5.38	AC50	4200	nM	CHEMBL_ACT_25217905
PPARG	5.3	AC50	5000	nM	CHEMBL_ACT_25113891
CYP2C9	5.3	Potency	5012	nM	CHEMBL_ACT_5041585
CYP2C9	5.3	AC50	5012	nM	CHEMBL_ACT_6014985
HTR2B	5.24	AC50	5771	nM	CHEMBL_ACT_25227313
HIF1A	5.2	Potency	6310	nM	CHEMBL_ACT_4129051
HIF1A	5.2	Potency	6310	nM	CHEMBL_ACT_4132630
HIF1A	5.2	Potency	6310	nM	CHEMBL_ACT_4519399
HIF1A	5.2	Potency	6310	nM	CHEMBL_ACT_4520873
SLC10A1	5.16	IC50	6900	nM	CHEMBL_ACT_19242119
SLC10A1	5.16	IC50	6900	nM	CHEMBL_ACT_24868560
HTR1A	5.15	AC50	7100	nM	CHEMBL_ACT_25215849
ADORA3	5.12	AC50	7572	nM	CHEMBL_ACT_25133980
ADRA2A	5.03	AC50	9300	nM	CHEMBL_ACT_25219678
HTR2A	5.02	AC50	9487	nM	CHEMBL_ACT_25224967
HSD17B10	5	Potency	10000	nM	CHEMBL_ACT_4841724

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

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
PHASE2	2
PHASE3	1
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05579327	PHASE3	COMPLETED	Withdrawal of Tiratricol Treatment in Males With Monocarboxylate Transporter 8 Deficiency (MCT8 Deficiency)
NCT02396459	PHASE2	ACTIVE_NOT_RECRUITING	Triac Trial II in MCT8 Deficiency Patients
NCT02060474	PHASE2	COMPLETED	Thyroid Hormone Analog Therapy in MCT8 Deficiency: Triac Trial Patients
NCT03783988	PHASE1	UNKNOWN	Study With a Topical Gel Containing TRIAC and DHEA in Subjects With Skin Atrophy Due to Glucocorticoids
NCT05911399	Not specified	AVAILABLE	Expanded Access Program for Tiratricol in Patients With Monocarboxylate Transporter 8 Deficiency

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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
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
DEXTROTHYROXINE	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