Propylthiouracil

Summary

Propylthiouracil (CHEMBL1518) is an approved small-molecule antithyroid drug (ATC H03BA02) targeting TPO and TAS2R38; indicated across 6 conditions including thyroid gland disorder and hyperthyroidism.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: H03BA02
• Targets: 2 (TPO, TAS2R38)
• Indications: 6 conditions
• Clinical trials: 8
• Chemistry: 170.23 Da · C7H10N2OS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1518
Name	Propylthiouracil
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	657298
ChEBI	CHEBI:8502
ATC	H03BA02
Molecular formula	C7H10N2OS
Molecular weight	170.23
InChIKey	KNAHARQHSZJURB-UHFFFAOYSA-N

SMILES: CCCC1=CC(=O)NC(=S)N1

IUPAC name: 6-propyl-2-sulfanylidene-1H-pyrimidin-4-one

ChEBI definition: A pyrimidinethione consisting of uracil in which the 2-oxo group is substituted by a thio group and the hydrogen at position 6 is substituted by a propyl group.

Pharmacological roles (ChEBI): antithyroid drug, carcinogenic agent, hormone antagonist, EC 1.14.13.39 (nitric oxide synthase) inhibitor, antioxidant, antidote to paracetamol poisoning.

Other ChEBI roles (chemical / environmental): antimetabolite.

Also known as: NSC-6498, NSC-70461, Propiltiouracilo, Propylthiouracil, Propylthiouracile, Propacil, Prothyran, Thyreostat ii, propylthiouracil, SID11112111, SID17389748, SID26751509

Patent coverage: 5,110 distinct patent families (15,046 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 14,944 (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
TPO	thyroid peroxidase	Inhibition			P07202
TAS2R38	TAS2R38	Agonist	5.68	0.1%	P59533

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Fructose-bisphosphate aldolase, 4’-phosphopantetheinyl transferase ffp, Thyroid peroxidase, Thyrotropin receptor, Myeloperoxidase, Cytochrome P450 2C19, Prostaglandin G/H synthase 1, Taste receptor type 2 member 38, Lactoperoxidase.

Bioactivity

ChEMBL activities: 10 potent at pChembl ≥ 5 of 13 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TAS2R38	5.7	EC50	2000	nM	CHEMBL_ACT_19334430
MPO	5.55	IC50	2810	nM	CHEMBL_ACT_15771996
CYP2C19	5.5	Potency	3162	nM	CHEMBL_ACT_4017455
TPO	5.47	IC50	3380	nM	CHEMBL_ACT_15771999
MPO	5.28	IC50	5250	nM	CHEMBL_ACT_25915679
MPO	5.24	IC50	5700	nM	CHEMBL_ACT_15772038
Q63921	5.18	AC50	6600	nM	CHEMBL_ACT_25174480
LPO	5.12	IC50	7520	nM	CHEMBL_ACT_25881961
TSHR	5	Potency	10000	nM	CHEMBL_ACT_3917432
TSHR	5	Potency	10000	nM	CHEMBL_ACT_4707217

Target pathways

Aggregated over 2 target gene(s): TPO, TAS2R38.

Top Reactome pathways

10 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	1	TAS2R38
Thyroxine biosynthesis	1	TPO
Signaling by GPCR	1	TAS2R38
GPCR downstream signalling	1	TAS2R38
G alpha (i) signalling events	1	TAS2R38
Class C/3 (Metabotropic glutamate/pheromone receptors)	1	TAS2R38
GPCR ligand binding	1	TAS2R38
Sensory Perception	1	TAS2R38
Sensory perception of taste	1	TAS2R38
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	TAS2R38

Dominant GO biological processes

GO term	Targets
thyroid hormone generation	1
response to oxidative stress	1
embryonic hemopoiesis	1
hormone biosynthetic process	1
hydrogen peroxide catabolic process	1
cellular oxidant detoxification	1
detection of chemical stimulus involved in sensory perception of bitter taste	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
sensory perception of taste	1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
thyroid gland disorder	4	MONDO:0003240	HP:0000820
hyperthyroidism	4	MONDO:0004425	EFO:0009189

2 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
thyrotoxicosis	3	MONDO:0010138	EFO:0009190
Graves disease	3	MONDO:0005364	EFO:0004237

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
Not specified	3
PHASE3	2
PHASE4	1
PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01056419	PHASE4	UNKNOWN	The Effect of Early Total Thyroidectomy in the Course of Graves’ Orbitopathy
NCT01436994	PHASE3	COMPLETED	Antithyroid Drug Treatment of Thyrotoxicosis in Young People
NCT05118542	PHASE3	COMPLETED	Effect of Hyperthyroidism and Its Treatment in Graves’ Disease to Early Marker of Atherosclerosis
NCT05762146	PHASE2	UNKNOWN	Networked Drug REpurposing for Mechanism-based neuroPrOtection in Acute Ischaemic STROKE
NCT04776499	PHASE1	COMPLETED	Possible Effects of Propylthiouracil, Riociguat and Perphenazine on Circulation of Healthy Volunteers
NCT00846755	Not specified	COMPLETED	Thyroid Disease in Pregnancy: Case Finding Versus Universal Screening
NCT03433352	Not specified	UNKNOWN	Intestinal Microbiota and Treatment of GD
NCT03447093	Not specified	UNKNOWN	The Oral Microbiota is Associated With Autoimmune Thyroiditis

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 6 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.

2 molecules share ≥1 primary target. Top 2 by shared-target count:

Molecule	Source	Status	Shared targets
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	TAS2R38
MITIPERSTAT	ChEMBL	Phase 2	TPO