Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4J8MF)

• DTT Name: Thyrotropin-releasing hormone receptor (TRHR)
• Synonyms: Thyroliberin receptor; TRH-R
• Gene Name: TRHR
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: TRFR_HUMAN
• TTD ID: T77796
• Sequence:
  MENETVSELNQTQLQPRAVVALEYQVVTILLVLIICGLGIVGNIMVVLVVMRTKHMRTPT
  NCYLVSLAVADLMVLVAAGLPNITDSIYGSWVYGYVGCLCITYLQYLGINASSCSITAFT
  IERYIAICHPIKAQFLCTFSRAKKIIIFVWAFTSLYCMLWFFLLDLNISTYKDAIVISCG
  YKISRNYYSPIYLMDFGVFYVVPMILATVLYGFIARILFLNPIPSDPKENSKTWKNDSTH
  QNTNLNVNTSNRCFNSTVSSRKQVTKMLAVVVILFALLWMPYRTLVVVNSFLSSPFQENW
  FLLFCRICIYLNSAINPVIYNLMSQKFRAAFRKLCNCKQKPTEKPANYSVALNYSVIKES
  DHFSTELDDITVTDTYLSATKVSFDDTCLASEVSFSQS
• Function: Receptor for thyrotropin-releasing hormone. This receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Peptide ligand-binding receptors (R-HSA-375276)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
protirelin	DMGN5QD	Central nervous system disease	8A04-8D87	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZETIRELIN	DMLY9F1	Pain	MG30-MG3Z	Phase 3	[2]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MONTIRELIN TETRAHYDRATE	DM31OGZ	Pain	MG30-MG3Z	Discontinued in Preregistration	[3]
Posatirelin	DML6EWH	Neurodegenerative disorder	8A20-8A23	Discontinued in Phase 3	[4]
JTP-2942	DM29C6S	Cognitive impairment	6D71	Discontinued in Phase 2	[5]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
C4X-101	DM5971G	Endocrine disease	5B3Z	Investigative	[6]
CORYMBONE B	DM463S2	Discovery agent	N.A.	Investigative	[7]
MeTRH	DMGH8WV	Discovery agent	N.A.	Investigative	[8]
MK-771	DM4YQV0	Discovery agent	N.A.	Investigative	[9]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Parkinson's disease	8A00.0	Substantia nigra tissue	2.98E-01	0.11	0.61

References

• [1] Company report (takeda)
• [2] Intestinal absorption of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue. II. In situ and in vitro absorption characteristics of azetirelin from the rat intestine. Biol Pharm Bull. 1995 Jul;18(7):976-9.
• [3] Montirelin hydrate (NS-3), a TRH analog, improved the disturbance of consciousness caused by head concussion and pentobarbital in mice. Nihon Yakurigaku Zasshi. 1996 May;107(5):237-45.
• [4] TRH analogs at Gedeon Richter Ltd.: highlights of experimental and clinical efficacy of posatirelin. Acta Pharm Hung. 2002;72(1):62-8.
• [5] Effect of JTP-2942, a novel thyrotropin-releasing hormone analogue, on pentobarbital-induced anesthesia in rats. Eur J Pharmacol. 1995 Mar 24;276(1-2):177-82.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 363).
• [7] Corymbones A and B, phloroglucinols with thyrotropin releasing hormone receptor 2 binding affinity from the flowers of Corymbia peltata. J Nat Prod. 2008 May;71(5):881-3.
• [8] Thyrotropin-releasing hormone receptor type 1 (TRH-R1), not TRH-R2, primarily mediates taltirelin actions in the CNS of mice. Neuropsychopharmacology. 2013 May;38(6):950-6.
• [9] TRH analog MK-771 reverses neurochemical and learning deficits in medial septal-lesioned rats. Peptides. 1989 Jan-Feb;10(1):121-4.