Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Follicle-stimulating hormone receptor (FSHR)
• Synonyms: LGR1; Follitropin receptor; FSH-R
• Gene Name: FSHR
• DTT Type: Successful target; [1]
• Related Disease: Female infertility [ICD-11: GA31]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: FSHR_HUMAN
• TTD ID: T68334
• Sequence:
  MALLLVSLLAFLSLGSGCHHRICHCSNRVFLCQESKVTEIPSDLPRNAIELRFVLTKLRV
  IQKGAFSGFGDLEKIEISQNDVLEVIEADVFSNLPKLHEIRIEKANNLLYINPEAFQNLP
  NLQYLLISNTGIKHLPDVHKIHSLQKVLLDIQDNINIHTIERNSFVGLSFESVILWLNKN
  GIQEIHNCAFNGTQLDELNLSDNNNLEELPNDVFHGASGPVILDISRTRIHSLPSYGLEN
  LKKLRARSTYNLKKLPTLEKLVALMEASLTYPSHCCAFANWRRQISELHPICNKSILRQE
  VDYMTQARGQRSSLAEDNESSYSRGFDMTYTEFDYDLCNEVVDVTCSPKPDAFNPCEDIM
  GYNILRVLIWFISILAITGNIIVLVILTTSQYKLTVPRFLMCNLAFADLCIGIYLLLIAS
  VDIHTKSQYHNYAIDWQTGAGCDAAGFFTVFASELSVYTLTAITLERWHTITHAMQLDCK
  VQLRHAASVMVMGWIFAFAAALFPIFGISSYMKVSICLPMDIDSPLSQLYVMSLLVLNVL
  AFVVICGCYIHIYLTVRNPNIVSSSSDTRIAKRMAMLIFTDFLCMAPISFFAISASLKVP
  LITVSKAKILLVLFHPINSCANPFLYAIFTKNFRRDFFILLSKCGCYEMQAQIYRTETSS
  TVHNTHPRNGHCSSAPRVTNGSTYILVPLSHLAQN
• Function: G protein-coupled receptor for follitropin, the follicle-stimulating hormone. Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways.
• KEGG Pathway:
  cAMP signaling pathway (hsa04024)
  Neuroactive ligand-receptor interaction (hsa04080)
  Ovarian steroidogenesis (hsa04913)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Hormone ligand-binding receptors (R-HSA-375281)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Follitropin beta	DM2JTS5	Female infertility	GA31.Z	Approved	[2]
Menotropins	DM4CF18	Female infertility	GA31.Z	Approved	[1]
Urofollitropin	DMG9HIA	Female infertility	GA31.Z	Approved	[3]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Suramin	DMTOUY9	African trypanosomiasis	1F51	Phase 1	[4], [5]

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
FSHR NAM	DMPRMOD	Contraception	QA21	Investigative	[6]
Long-acting FSH conjugate	DMD32IN	Female infertility	GA31.Z	Investigative	[6]
PRX-111	DMSPH30	Female infertility	GA31.Z	Investigative	[7]
Recombinant follicle stimulating hormone	DMNHOI3	Female infertility	GA31.Z	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Ovarian cancer	2C82	Ovarian tissue	1.56E-02	-0.56	-1.34

References

• [1] The role of gonadotropins in ovulation induction. Am J Obstet Gynecol. 1995 Feb;172(2 Pt 2):759-65.
• [2] Follitropin-alpha (Gonal-F) versus follitropin-beta (Puregon) in controlled ovarian hyperstimulation for in vitro fertilization: is there any diffe... Fertil Steril. 2009 Apr;91(4 Suppl):1522-5.
• [3] Follicle-stimulating hormone in clinical practice: an update. Treat Endocrinol. 2004;3(3):161-71.
• [4] Suramin: clinical uses and structure-activity relationships. Mini Rev Med Chem. 2008 Nov;8(13):1384-94.
• [5] Follicle stimulating hormone receptor (FSHR) antagonist and epithelial ovarian cancer (EOC). J Exp Ther Oncol. 2007;6(3):201-4.
• [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: 253).
• [7] A naturally occurring basically charged human follicle-stimulating hormone (FSH) variant inhibits FSH-induced androgen aromatization and tissue-type plasminogen activator enzyme activity in vitro. Neuroendocrinology. 1998 Mar;67(3):153-63.