Target Information

Target General Infomation
Target ID
T75797
Former ID
TTDS00169
Target Name
Prostaglandin F2-alpha receptor
Gene Name
PTGFR
Synonyms
FP prostaglandin receptor; FP prostanoid receptor; PGF receptor; PGF2 alpha receptor; Prostanoid FP receptor; PTGFR
Target Type
Successful
Disease Alzheimer disease [ICD9: 331; ICD10: G30]
Aborting pregnancy [ICD9: 779.6; ICD10: O04]
Dysmenorrhea [ICD9: 625.3; ICD10: N94.4-N94.6]
Glaucoma [ICD9: 365; ICD10: H40-H42]
Open-angle glaucoma; Ocular hypertension [ICD9: 365, 365.04; ICD10: H40-H42, H40.0]
Ocular disease [ICD10: H00-H59]
Renal cancer [ICD9: 140-229, 189; ICD10: C64]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Receptor for prostaglandin F2-alpha (PGF2-alpha). The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. Initiates luteolysis in the corpus luteum (By similarity). 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.
BioChemical Class
GPCR rhodopsin
Target Validation
T75797
UniProt ID
P43088
Sequence
MSMNNSKQLVSPAAALLSNTTCQTENRLSVFFSVIFMTVGILSNSLAIAILMKAYQRFRQ
KSKASFLLLASGLVITDFFGHLINGAIAVFVYASDKEWIRFDQSNVLCSIFGICMVFSGL
CPLLLGSVMAIERCIGVTKPIFHSTKITSKHVKMMLSGVCLFAVFIALLPILGHRDYKIQ
ASRTWCFYNTEDIKDWEDRFYLLLFSFLGLLALGVSLLCNAITGITLLRVKFKSQQHRQG
RSHHLEMVIQLLAIMCVSCICWSPFLVTMANIGINGNHSLETCETTLFALRMATWNQILD
PWVYILLRKAVLKNLYKLASQCCGVHVISLHIWELSSIKNSLKVAAISESPVAEKSAST
Drugs and Mode of Action
Drug(s) Carboprost Tromethamine Drug Info Approved Aborting pregnancy [1]
Latanoprost Drug Info Approved Open-angle glaucoma; Ocular hypertension [2], [3]
Tafluprost Drug Info Approved Glaucoma [4], [5], [6], [7]
Travoprost Drug Info Approved Open-angle glaucoma; Ocular hypertension [2], [8]
LAROPIPRANT Drug Info Phase 4 Discovery agent [9], [10]
BOL-303259-X Drug Info Phase 3 Renal cancer [11]
PGF2ALPHA-IE Drug Info Phase 3 Glaucoma [12]
Latanoprost Drug Info Phase 2 Glaucoma [13]
ONO-9054 Drug Info Phase 2 Glaucoma [14]
Latanoprost Drug Info Phase 1/2 Glaucoma [15]
PDC-41 Drug Info Phase 1 Dysmenorrhea [16]
bimatoprost (free acid form) Drug Info Clinical trial Alzheimer disease [17]
PGF2alpha Drug Info Clinical trial Solid tumours [18]
Agonist 13,14-dihydro-16-m-chlorophenoxy-w-tetranor-PGF1alpha Drug Info [19]
AL-8810 Drug Info [20]
AL12180 Drug Info [21]
bimatoprost (free acid form) Drug Info [22]
BOL-303259-X Drug Info [23]
carbacyclin Drug Info [24]
cloprostenol Drug Info [24]
fluprostenol Drug Info [25]
I-BOP Drug Info [25]
Latanoprost Drug Info [26]
M&B 28767 Drug Info [25]
PGD2 Drug Info [25]
PGF2alpha Drug Info [27]
Travoprost Drug Info [28]
U46619 Drug Info [24]
[3H](+)-fluprostenol Drug Info [29]
[3H]PGF2alpha Drug Info [30]
Antagonist AS604872 Drug Info [31]
PDC-31 Drug Info [29]
PDC-41 Drug Info [32]
Modulator Carboprost Tromethamine Drug Info [33]
H2S-releasing latanoprost Drug Info [29]
NCX-125 Drug Info [29]
ONO-9054 Drug Info [14]
PGF2ALPHA-IE Drug Info [34], [7]
Tafluprost Drug Info [7]
Inhibitor LAROPIPRANT Drug Info [35]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Calcium signaling pathway
Neuroactive ligand-receptor interaction
Reactome Prostanoid ligand receptors
G alpha (q) signalling events
WikiPathways Prostaglandin Synthesis and Regulation
GPCRs, Class A Rhodopsin-like
Gastrin-CREB signalling pathway via PKC and MAPK
Small Ligand GPCRs
GPCR ligand binding
GPCR downstream signaling
GPCRs, Other
References
REF 1FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 017989.
REF 2Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
REF 3(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. (Ligand id: 1961).
REF 4Mol Endocrinol. 2010 Feb;24(2):436-46. Epub 2010 Jan 5.Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin receptor phosphorylation.
REF 5Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
REF 6(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. (Ligand id: 7451).
REF 7Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
REF 8(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. (Ligand id: 7102).
REF 9ClinicalTrials.gov (NCT01126073) Niacin/Laropiprant and Endothelial Function. U.S. National Institutes of Health.
REF 10(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. (Ligand id: 3356).
REF 11ClinicalTrials.gov (NCT01895972) A Study Evaluating the Long-Term Safety of Latanoprostene Bunod Ophthalmic Solution 0.024%, in Japanese Subjects With Open-Angle Glaucoma or Ocular Hypertension. U.S.National Institutes of Health.
REF 12The effect of prostaglandin F2 alpha-1-isopropylester (PGF2 alpha-IE) on uveoscleral outflow. Prog Clin Biol Res. 1989;312:429-36.
REF 13Clinical pipeline report, company report or official report of Mati therapeutics.
REF 14IOP-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.
REF 15Clinical pipeline report, company report or official report of Pfizer.
REF 16ClinicalTrials.gov (NCT01250587) Dose-Finding Study of PDC31 in Patients With Primary Dysmenorrhea. U.S. National Institutes of Health.
REF 17(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. (Ligand id: 1959).
REF 18Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81.
REF 19J Med Chem. 2000 Mar 9;43(5):945-52.Design and synthesis of 13,14-dihydro prostaglandin F(1alpha) analogues as potent and selective ligands for the human FP receptor.
REF 20AL-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.
REF 21Preclinical pharmacology of AL-12182, a new ocular hypotensive 11-oxa prostaglandin analog. J Ocul Pharmacol Ther. 2006 Oct;22(5):291-309.
REF 22Replacement 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.
REF 23Ocular 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.
REF 24The 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.
REF 25Ligand 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.
REF 26PGF(2alpha) FP Receptor Contributes to Brain Damage Following Transient Focal Brain Ischemia. Neurotox Res. 2009 Jan;15(1):62-70. Epub 2009 Feb 11.
REF 27Identification 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.
REF 28Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys. J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8.
REF 29(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).
REF 30Cloning and expression of a cDNA for the human prostanoid FP receptor. J Biol Chem. 1994 Jan 28;269(4):2632-6.
REF 31Arrest 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.
REF 32THG113: a novel selective FP antagonist that delays preterm labor. Semin Perinatol. 2002 Dec;26(6):389-97.
REF 33Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
REF 34Role of nitric oxide in PGF2 alpha-induced ocular hyperemia. Exp Eye Res. 1994 Oct;59(4):401-7.
REF 35J Med Chem. 2007 Feb 22;50(4):794-806.Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524).

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