Protirelin

Summary

Protirelin (CHEMBL1472) is an approved protein (ATC V04CJ02) targeting TRHR; indicated across 2 conditions including acute respiratory distress syndrome and neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Protein
• ATC class: V04CJ02
• Targets: 1 (TRHR)
• Indications: 2 conditions
• Clinical trials: 4
• Chemistry: 362.38 Da · C16H22N6O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1472
Name	Protirelin
Type	Protein
Max phase	4
FDA approved	yes
PubChem CID	638678
ChEBI	CHEBI:35940
ATC	V04CJ02
Molecular formula	C16H22N6O4
Molecular weight	362.38
InChIKey	XNSAINXGIQZQOO-SRVKXCTJSA-N

SMILES: C1C[C@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@@H]3CCC(=O)N3)C(=O)N

IUPAC name: (2S)-N-[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide

ChEBI definition: A tripeptide composed of L-pyroglutamyl, L-histidyl and L-prolinamide residues joined in sequence.

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

Also known as: A-38579, ABBOTT-38579, Lopremone, NSC-760113, Protirelin, Protirelin tartrate, synthetic, Protirelina, Protireline, Relefact trh, SYNTHETIC TRH, Thypinone

Patent coverage: 5,289 distinct patent families (13,012 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 10,992 (84%) 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
TRHR	TRH1 receptor	Full agonist	7.4	0%	P34981
	TRH2 receptor	Full agonist	7.4

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Thyrotropin-releasing hormone receptor, Thyrotropin-releasing hormone receptor, Thyrotropin-releasing hormone receptor.

Bioactivity

ChEMBL activities: 14 potent at pChembl ≥ 5 of 14 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P21761	9.31	EC50	0.49	nM	CHEMBL_ACT_969819
P21761	9.17	EC50	0.68	nM	CHEMBL_ACT_1182931
P21761	9	EC50	1	nM	CHEMBL_ACT_15671048
P21761	9	EC50	1	nM	CHEMBL_ACT_16511163
P21761	8.59	IC50	2.6	nM	CHEMBL_ACT_15671016
Q01717	8.52	EC50	3	nM	CHEMBL_ACT_1609742
TRHR	8.52	EC50	3	nM	CHEMBL_ACT_1852886
P21761	8.49	EC50	3.2	nM	CHEMBL_ACT_16511209
P21761	8	Ki	10	nM	CHEMBL_ACT_1182930
Q01717	7.7	Ki	20	nM	CHEMBL_ACT_1609739
TRHR	7.7	Ki	20	nM	CHEMBL_ACT_1852846
P21761	7.64	Ki	23	nM	CHEMBL_ACT_969818
P21761	7.58	IC50	26	nM	CHEMBL_ACT_16511126
Q01717	7.37	Ki	42.3	nM	CHEMBL_ACT_1488879

Target pathways

Aggregated over 1 target gene(s): TRHR.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	1	TRHR
G alpha (q) signalling events	1	TRHR

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
signal transduction	1

Indications & clinical

Indications

2 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).

Indication	Trial phase	MONDO	EFO
acute respiratory distress syndrome	3	MONDO:0006502	EFO:1000637
neoplasm	2	MONDO:0005070	MONDO:0004992

Clinical trials

Total trials: 4.

Phase distribution

Phase	Trials
Not specified	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00004778	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Antenatal Thyrotropin-Releasing Hormone in Pregnant Women With Threatened Premature Delivery
NCT00004840	Not specified	COMPLETED	Study of Antenatal Thyrotropin-Releasing Hormone in Women in Premature Labor to Prevent Lung Disease in Preterm Infants
NCT02399475	Not specified	COMPLETED	Mechanistic Study of Subclinical Hypothyroidism In the Elderly
NCT04767763	Not specified	COMPLETED	Thyroid Function in Critically Ill Patients With Acute Kidney Injury

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

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).