Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT8R70G)

• DTT Name: Gonadotropin-releasing hormone receptor (GNRHR)
• Synonyms: Hypothalamic gonadotropin-releasing hormone receptor; Gonadotrophin releasing hormone receptor; GnRH-R; GnRH receptor; GRHR
• Gene Name: GNRHR
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: GNRHR_HUMAN
• TTD ID: T12475
• Sequence:
  MANSASPEQNQNHCSAINNSIPLMQGNLPTLTLSGKIRVTVTFFLFLLSATFNASFLLKL
  QKWTQKKEKGKKLSRMKLLLKHLTLANLLETLIVMPLDGMWNITVQWYAGELLCKVLSYL
  KLFSMYAPAFMMVVISLDRSLAITRPLALKSNSKVGQSMVGLAWILSSVFAGPQLYIFRM
  IHLADSSGQTKVFSQCVTHCSFSQWWHQAFYNFFTFSCLFIIPLFIMLICNAKIIFTLTR
  VLHQDPHELQLNQSKNNIPRARLKTLKMTVAFATSFTVCWTPYYVLGIWYWFDPEMLNRL
  SDPVNHFFFLFAFLNPCFDPLIYGYFSL
• Function: Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol-calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  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

10 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Abarelix	DM5WFNP	Prostate cancer	2C82.0	Approved	[2]
Cetrorelix	DMFD9Q6	Ovarian stimulation	LB45.1	Approved	[1]
Degarelix	DM3O8QY	Prostate cancer	2C82.0	Approved	[3]
Elagolix sodium	DMRDUC0	Endometriosis	GA10	Approved	[4]
Ganirelix	DMGMB30	Ovulation dysfunction	5A80	Approved	[5]
Gonadorelin	DMAQ469	Amenorrhea	GA20.0	Approved	[6]
Leuprorelin acetate	DM15HAT	Prostate cancer	2C82.0	Approved	[7]
Nafarelin	DMAHEFY	Endometriosis	GA10	Approved	[8]
Relugolix	DMK7IWL	Prostate cancer	2C82.0	Approved	[9]
Triptorelin	DMTK4LS	Infertility	GB04	Approved	[10]

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AEZS-108	DMAYO46	Acute lymphoblastic leukaemia	2A85	Phase 3	[11]
Elagolix	DMB2C0E	Uterine fibroids	2E86.0	Phase 3	[12]
GnRH	DM0LQ94	Female infertility	GA31.Z	Phase 3	[13]
ACYLINE	DM9GRTK	Prostate cancer	2C82.0	Phase 2	[14]
ASP-1707	DME8XD7	Endometriosis	GA10	Phase 2	[15]
KLH-2109	DM40HOY	Endometriosis	GA10	Phase 2	[16]
Ozarelix	DMEGTH1	Prostate disease	GA91	Phase 2	[17]
PEP-223/CoVaccine HT	DMM9L1R	Prostate cancer	2C82.0	Phase 1/2	[13]
Prostate cancer vaccine	DMRSRBL	Prostate cancer	2C82.0	Phase 1/2	[13]
VERU-100	DMYXE9C	Prostate cancer	2C82.0	Phase 1/2	[18]

8 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Antide	DMEO6PR	Prostate hyperplasia	GA90	Discontinued in Phase 2	[19]
Gonadimmune	DM9MEAY	Prostate cancer	2C82.0	Discontinued in Phase 2	[20]
TAK-013	DM0TDZI	Uterine fibroids	2E86.0	Discontinued in Phase 2	[21]
A-75998	DM0DLC1	Hormone deficiency	5A61.1	Discontinued in Phase 1	[22]
NBI-42902	DM4MTPU	Prostate cancer	2C82.0	Discontinued in Phase 1	[23]
Ramorelix	DMVID8E	Esophageal cancer	2B70	Discontinued in Phase 1	[24]
D-21775	DME07ML	Solid tumour/cancer	2A00-2F9Z	Terminated	[13]
D-26344	DMBJAUC	Solid tumour/cancer	2A00-2F9Z	Terminated	[26]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
5-(N,N-hexamethylene)-amiloride	DMC4IUQ	Coronavirus infection	1D92	Preclinical	[25]

48 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AEZS-115	DMULWOG	Solid tumour/cancer	2A00-2F9Z	Investigative	[13]
AN-207	DMRS0LA	Solid tumour/cancer	2A00-2F9Z	Investigative	[13]
antarelix	DM7TOGW	Discovery agent	N.A.	Investigative	[27]
AZALINE B	DMN861Q	Discovery agent	N.A.	Investigative	[14]
detirelix	DMFWDNJ	Discovery agent	N.A.	Investigative	[28]
FD-1	DM7IEL2	Discovery agent	N.A.	Investigative	[25]
furan-1	DMCFEBW	Discovery agent	N.A.	Investigative	[29]
IN-3	DMENHMU	Discovery agent	N.A.	Investigative	[30]
LHRH	DMB4ACY	Endometriosis	GA10	Investigative	[31]
LXT-101	DM0LKPE	Prostate cancer	2C82.0	Investigative	[32]
Org-30850	DMXGA56	Discovery agent	N.A.	Investigative	[33]
PGlu-His-Trp-Ser-His-D-Tyr-Leu-Arg-Pro-Gly-NH2	DMLMTIY	Discovery agent	N.A.	Investigative	[34]
PGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2	DM40PT5	Discovery agent	N.A.	Investigative	[34]
T-98475	DMFKQ1W	Discovery agent	N.A.	Investigative	[21]
WAY-207024	DMJ14NE	Discovery agent	N.A.	Investigative	[35]
[125I]cetrorelix	DM0X824	Discovery agent	N.A.	Investigative	[36]
[4Aph(CO-(C2H4O)3-C2H4-NH-CO-NH-OCH3)5]degarelix	DM86Z4H	Discovery agent	N.A.	Investigative	[37]
[4Aph(CO-NH-(C2H4O)2-C2H5)5]degarelix	DM4IXJA	Discovery agent	N.A.	Investigative	[37]
[4Aph(CO-NH-OCH3)5,D-4Aph(CO-NH-OCH3)6]degarelix	DM57TIU	Discovery agent	N.A.	Investigative	[37]
[4Aph(CO-NH-OCH3)5]degarelix	DM6C8K1	Discovery agent	N.A.	Investigative	[37]
[4Aph(CO-NH-OH)5]degarelix	DMFMB31	Discovery agent	N.A.	Investigative	[37]
[D-4Aph(CO-NH-(C2H4O)2-C2H5)6]degarelix	DMFKTJ8	Discovery agent	N.A.	Investigative	[37]
[D-4Aph(CO-NH-OCH3)6]degarelix	DMR7TEQ	Discovery agent	N.A.	Investigative	[37]
[D-4Aph(CO-NH-OH)6]degarelix	DMMVIX7	Discovery agent	N.A.	Investigative	[37]
[D-Dab(CO-NH-OCH3)3]degarelix	DMEZKX0	Discovery agent	N.A.	Investigative	[37]
[D-Dab(CO-NH-OH)3]degarelix	DMRVPN1	Discovery agent	N.A.	Investigative	[37]
[D-Dap(CO-NH-OCH3)3]degarelix	DM5ZR4S	Discovery agent	N.A.	Investigative	[37]
[D-Dap(CO-NH-OH)3]degarelix	DMS0LFT	Discovery agent	N.A.	Investigative	[37]
[D-Gln3,D-Ncy(isopropyl)7]acyline	DMP1D7Q	Discovery agent	N.A.	Investigative	[14]
[D-Gln3,D-Ncy(SO,isopropyl)7]acyline	DMFAX1Q	Discovery agent	N.A.	Investigative	[14]
[D-Gln3,D-Ncy(SO2,isopropyl)7]acyline	DM3H0CX	Discovery agent	N.A.	Investigative	[14]
[D-Gln3,Ncy(isopropyl)7]acyline	DMMEQ3R	Discovery agent	N.A.	Investigative	[14]
[D-Gln3,Ncy(SO,isopropyl)7]acyline	DM2QDXW	Discovery agent	N.A.	Investigative	[14]
[D-Gln3,Ncy(SO2,isopropyl)7]acyline	DMJSCO7	Discovery agent	N.A.	Investigative	[14]
[D-Ncy(2-naphthyl)1]acyline	DMAFNTL	Discovery agent	N.A.	Investigative	[14]
[D-Ncy(isopropyl)7]acyline	DMVBTAM	Discovery agent	N.A.	Investigative	[14]
[D-Ncy(methyl)10] acyline	DM9TORW	Discovery agent	N.A.	Investigative	[14]
[D-Ncy(methyl)4]acyline	DM63FN5	Discovery agent	N.A.	Investigative	[14]
[D-Ncy(SO,isopropyl)7]acyline	DME9AN4	Discovery agent	N.A.	Investigative	[14]
[D-Ncy(SO,methyl)10]acyline	DMT2X98	Discovery agent	N.A.	Investigative	[14]
[D-Ncy(SO,methyl)4]acyline	DM6HEXG	Discovery agent	N.A.	Investigative	[14]
[Ncy(2-naphthyl)1]acyline	DME6LKY	Discovery agent	N.A.	Investigative	[14]
[Ncy(isopropyl)7]acyline	DM5CS8U	Discovery agent	N.A.	Investigative	[14]
[Ncy(methyl)10]acyline	DM9RC3O	Discovery agent	N.A.	Investigative	[14]
[Ncy(methyl)4]acyline	DMLK8YQ	Discovery agent	N.A.	Investigative	[14]
[Ncy(SO,isopropyl)7]acyline	DMEFIQ9	Discovery agent	N.A.	Investigative	[14]
[Ncy(SO,methyl)10]acyline	DMT8X45	Discovery agent	N.A.	Investigative	[14]
[Ncy(SO,methyl)4]acyline	DM057MP	Discovery agent	N.A.	Investigative	[14]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Endometriosis	GA10	Endometrium tissue	9.07E-01	0.02	0.09
Prostate cancer	2C82	Prostate	4.30E-01	1.33E-02	0.04

References

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