Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT3KBZY)

• DTT Name: G-protein coupled receptor 54 (KISS1R)
• Synonyms: KiSS-1 receptor GPR54; KISS1R; GPR54
• Gene Name: KISS1R
• DTT Type: Discontinued target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: KISSR_HUMAN
• TTD ID: T39123
• Sequence:
  MHTVATSGPNASWGAPANASGCPGCGANASDGPVPSPRAVDAWLVPLFFAALMLLGLVGN
  SLVIYVICRHKPMRTVTNFYIANLAATDVTFLLCCVPFTALLYPLPGWVLGDFMCKFVNY
  IQQVSVQATCATLTAMSVDRWYVTVFPLRALHRRTPRLALAVSLSIWVGSAAVSAPVLAL
  HRLSPGPRAYCSEAFPSRALERAFALYNLLALYLLPLLATCACYAAMLRHLGRVAVRPAP
  ADSALQGQVLAERAGAVRAKVSRLVAAVVLLFAACWGPIQLFLVLQALGPAGSWHPRSYA
  AYALKTWAHCMSYSNSALNPLLYAFLGSHFRQAFRRVCPCAPRRPRRPRRPGPSDPAAPH
  AELLRLGSHPAPARAQKPGSSGLAARGLCVLGEDNAPL
• Function: Receptor for metastin(kisspeptin-54 or kp-54), a C- terminally amidated peptide of KiSS1. KiSS1 is a metastasis suppressor protein that suppresses metastases in malignant melanomas and in some breast carcinomas without affecting tumorigenicity. The metastasis suppressor properties may be mediated in part by cell cycle arrest and induction of apoptosis in malignant cells. The receptor is essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/KISS1R system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. The receptor is also probably involved in the regulation and fine- tuning of trophoblast invasion generated by the trophoblast itself. Analysis of the transduction pathways activated by the receptor identifies couplingto phospholipase C and intracellular calcium release through pertussis toxin-insensitive G(q) proteins.
• KEGG Pathway: 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 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TAK-683	DMRD8HK	Prostate cancer	2C82.0	Discontinued in Phase 1	[1]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-fluorobenzoyl-Phe-Gly-Leu-Arg-Trp-NH2	DMWD42N	Discovery agent	N.A.	Investigative	[2]
kisspeptin-10	DMDL21W	Discovery agent	N.A.	Investigative	[3]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	2.51E-03	0.74	0.91

References

• [1] Clinical pipeline report, company report or official report of Takeda (2009).
• [2] Development of novel G-protein-coupled receptor 54 agonists with resistance to degradation by matrix metalloproteinase. J Med Chem. 2008 Dec 11;51(23):7645-9.
• [3] The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001 Sep 14;276(37):34631-6.