Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT0ID4A)

• DTT Name: Leutinizing-hormone-releasing hormone (GNRH1)
• Synonyms: Progonadoliberin-1; Progonadoliberin I; LHRH; GRH; GNRH
• Gene Name: GNRH1
• DTT Type: Successful target; [1]
• BioChemical Class: Gonadotropin-releasing hormone
• UniProt ID: GON1_HUMAN
• TTD ID: T18950
• Sequence:
  MKPIQKLLAGLILLTWCVEGCSSQHWSYGLRPGGKRDAENLIDSFQEIVKEVGQLAETQR
  FECTTHQPRSPLRDLKGALESLIEEETGQKKI
• Function: Stimulates the secretion of gonadotropins; it stimulates the secretion of both luteinizing and follicle-stimulating hormones.
• KEGG Pathway: GnRH signaling pathway (hsa04912)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Hormone ligand-binding receptors (R-HSA-375281)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Goserelin	DMAT8CG	Breast cancer	2C60-2C65	Approved	[2]
Leuprolide	DM5XPIJ	Plasma cell myeloma	2A83.1	Approved	[1]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NAL-GLU	DMD5AEB	Prostate cancer	2C82.0	Phase 2/3	[3]
CG201	DMWY609	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Norelin	DMYCLZR	Prostate cancer	2C82.0	Discontinued in Phase 2	[5]
TAK-810	DMCFOSG	Prostate cancer	2C82.0	Discontinued in Phase 1	[6]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anti-GnRH Spiegelmer	DM4HKC8	Discovery agent	N.A.	Investigative	[7]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	2.23E-01	0.04	0.06

References

• [1] Increased risk of metabolic syndrome, diabetes mellitus, and cardiovascular disease in men receiving androgen deprivation therapy for prostate cancer. Pharmacotherapy. 2008 Dec;28(12):1511-22.
• [2] Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):341-9.
• [3] The gonadotropin-releasing hormone antagonist (Nal-Glu) acutely blocks the luteinizing hormone surge but allows for resumption of folliculogenesis in normal women. Am J Obstet Gynecol. 1991 Dec;165(6Pt 1):1811-7.
• [4] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011623)
• [6] EP patent application no. 2018865, Combination comprising n-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[1,3,4-oxadiazol-2-yl]phenyl)pyridine-3-sulphonamide and an lhrh analogue and/or a bisphosphonate.
• [7] In vivo properties of an anti-GnRH Spiegelmer: an example of an oligonucleotide-based therapeutic substance class. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8898-902.