Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTT2ZAR)

• DTT Name: Prostaglandin F2-alpha receptor (PTGFR)
• Synonyms: Prostanoid FP receptor; PGF2-alpha receptor; PGF2 alpha receptor; PGF receptor; FP prostanoid receptor; FP prostaglandin receptor
• Gene Name: PTGFR
• DTT Type: Successful target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: PF2R_HUMAN
• TTD ID: T75797
• Sequence:
  MSMNNSKQLVSPAAALLSNTTCQTENRLSVFFSVIFMTVGILSNSLAIAILMKAYQRFRQ
  KSKASFLLLASGLVITDFFGHLINGAIAVFVYASDKEWIRFDQSNVLCSIFGICMVFSGL
  CPLLLGSVMAIERCIGVTKPIFHSTKITSKHVKMMLSGVCLFAVFIALLPILGHRDYKIQ
  ASRTWCFYNTEDIKDWEDRFYLLLFSFLGLLALGVSLLCNAITGITLLRVKFKSQQHRQG
  RSHHLEMVIQLLAIMCVSCICWSPFLVTMANIGINGNHSLETCETTLFALRMATWNQILD
  PWVYILLRKAVLKNLYKLASQCCGVHVISLHIWELSSIKNSLKVAAISESPVAEKSAST
• Function: The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum. Isoforms 2 to 7 do not bind PGF2-alpha but are proposed to modulate signaling by participating in variant receptor complexes; heterodimers between isoform 1 and isoform 5 are proposed to be a receptor for prostamides including the synthetic analog bimatoprost. Receptor for prostaglandin F2-alpha (PGF2-alpha).
• KEGG Pathway:
  Calcium signaling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (q) signalling events (R-HSA-416476)
  Prostanoid ligand receptors (R-HSA-391908)

Molecular Interaction Atlas (MIA) of This DTT

7 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BOL-303259-X	DM2EXC5	Open-angle glaucoma	9C61	Approved	[2]
Carboprost Tromethamine	DMS3508	Abortion	JA00	Approved	[3]
Dinoprostone	DMTYOPD	Medical abortion	JA00.1Z	Approved	[4]
Latanoprost	DMI5OXG	Ocular hypertension	9C61.01	Approved	[5]
Tafluprost	DMFC41K	Glaucoma/ocular hypertension	9C61	Approved	[6]
Travoprost	DM20K91	Ocular hypertension	9C61.01	Approved	[1]
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[7]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PGF2ALPHA-IE	DM5DAP3	Glaucoma/ocular hypertension	9C61	Phase 3	[8]
ONO-9054	DM5O6GC	Glaucoma/ocular hypertension	9C61	Phase 2	[9]
PDC-41	DM74YO8	Dysmenorrhea	GA34.3	Phase 1	[10]
bimatoprost (free acid form)	DM531SA	Alzheimer disease	8A20	Clinical trial	[11]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[12]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BUTAPROST	DMVYNJZ	Discovery agent	N.A.	Patented	[4]

14 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
13,14-dihydro-16-m-chlorophenoxy-w-tetranor-PGF1alpha	DMNRMTX	Discovery agent	N.A.	Investigative	[13]
AL-8810	DMRWLQM	Discovery agent	N.A.	Investigative	[14]
AL12180	DM0JE4N	Discovery agent	N.A.	Investigative	[15]
AS604872	DM9V5GS	Discovery agent	N.A.	Investigative	[16]
carbacyclin	DMMBQYE	Discovery agent	N.A.	Investigative	[17]
cloprostenol	DMH01JV	Discovery agent	N.A.	Investigative	[17]
fluprostenol	DM9Q2PG	Discovery agent	N.A.	Investigative	[18]
I-BOP	DMJAPML	Discovery agent	N.A.	Investigative	[18]
M&B 28767	DMJQG82	Discovery agent	N.A.	Investigative	[18]
NCX-125	DMYBWXR	Glaucoma/ocular hypertension	9C61	Investigative	[19]
PDC-31	DMUDY7H	Dysmenorrhea	GA34.3	Investigative	[19]
PGD2	DMYDW6J	Discovery agent	N.A.	Investigative	[18]
U46619	DM13FX4	Discovery agent	N.A.	Investigative	[17]
[3H]PGF2alpha	DMPE1B2	Discovery agent	N.A.	Investigative	[20]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Renal cancer	2C82	Kidney	2.69E-01	-0.47	-0.84
Alzheimer's disease	8A00.0	Entorhinal cortex	8.25E-02	-0.05	-0.14

References

• [1] Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys. J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8.
• [2] Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2alpha agonist, in preclinical models. Exp Eye Res. 2011 Sep;93(3):250-5.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Evaluation of WO 2012/177618 A1 and US-2014/0179750 A1: novel small molecule antagonists of prostaglandin-E2 receptor EP2.Expert Opin Ther Pat. 2015 Jul;25(7):837-44.
• [5] PGF(2alpha) FP receptor contributes to brain damage following transient focal brain ischemia. Neurotox Res. 2009 Jan;15(1):62-70.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [7] Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydroc... J Med Chem. 2007 Feb 22;50(4):794-806.
• [8] Role of nitric oxide in PGF2 alpha-induced ocular hyperemia. Exp Eye Res. 1994 Oct;59(4):401-7.
• [9] IOP-Lowering Effect of ONO-9054, A Novel Dual Agonist of Prostanoid EP3 and FP Receptors, in Monkeys. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2547-52.
• [10] THG113: a novel selective FP antagonist that delays preterm labor. Semin Perinatol. 2002 Dec;26(6):389-97.
• [11] Replacement of the carboxylic acid group of prostaglandin f(2alpha) with a hydroxyl or methoxy substituent provides biologically unique compounds. Br J Pharmacol. 2000 Aug;130(8):1933-43.
• [12] Identification by site-directed mutagenesis of amino acids contributing to ligand-binding specificity or signal transduction properties of the human FP prostanoid receptor. Biochem J. 2003 Apr 15;371(Pt 2):443-9.
• [13] Design and synthesis of 13,14-dihydro prostaglandin F(1alpha) analogues as potent and selective ligands for the human FP receptor. J Med Chem. 2000 Mar 9;43(5):945-52.
• [14] AL-8810: a novel prostaglandin F2 alpha analog with selective antagonist effects at the prostaglandin F2 alpha (FP) receptor. J Pharmacol Exp Ther. 1999 Sep;290(3):1278-84.
• [15] Preclinical pharmacology of AL-12182, a new ocular hypotensive 11-oxa prostaglandin analog. J Ocul Pharmacol Ther. 2006 Oct;22(5):291-309.
• [16] Arrest of preterm labor in rat and mouse by an oral and selective nonprostanoid antagonist of the prostaglandin F2alpha receptor (FP). Am J Obstet Gynecol. 2007 Jul;197(1):54.e1-9.
• [17] The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta. 2000 Jan 17;1483(2):285-93.
• [18] Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997 Sep;122(2):217-24.
• [19] 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: 344).
• [20] Cloning and expression of a cDNA for the human prostanoid FP receptor. J Biol Chem. 1994 Jan 28;269(4):2632-6.