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 [538496]
Latanoprost Drug Info Approved Open-angle glaucoma; Ocular hypertension [536361], [539258]
Tafluprost Drug Info Approved Glaucoma [530618], [532210], [542476], [551871]
Travoprost Drug Info Approved Open-angle glaucoma; Ocular hypertension [536361], [542110]
LAROPIPRANT Drug Info Phase 4 Discovery agent [523049], [540312]
BOL-303259-X Drug Info Phase 3 Renal cancer [524354]
PGF2ALPHA-IE Drug Info Phase 3 Glaucoma [533334]
Latanoprost Drug Info Phase 2 Glaucoma [551115]
ONO-9054 Drug Info Phase 2 Glaucoma [533184]
Latanoprost Drug Info Phase 1/2 Glaucoma [551493]
PDC-41 Drug Info Phase 1 Dysmenorrhea [523270]
bimatoprost (free acid form) Drug Info Clinical trial Alzheimer disease [539256]
PGF2alpha Drug Info Clinical trial Solid tumours [532003]
Agonist 13,14-dihydro-16-m-chlorophenoxy-w-tetranor-PGF1alpha Drug Info [525721]
AL-8810 Drug Info [525568]
AL12180 Drug Info [528506]
bimatoprost (free acid form) Drug Info [525853]
BOL-303259-X Drug Info [531388]
carbacyclin Drug Info [525673]
cloprostenol Drug Info [525673]
fluprostenol Drug Info [534478]
I-BOP Drug Info [534478]
Latanoprost Drug Info [537255]
M&B 28767 Drug Info [534478]
PGD2 Drug Info [534478]
PGF2alpha Drug Info [526505]
Travoprost Drug Info [537092]
U46619 Drug Info [525673]
[3H](+)-fluprostenol Drug Info [543781]
[3H]PGF2alpha Drug Info [533982]
Antagonist AS604872 Drug Info [528941]
PDC-31 Drug Info [543781]
PDC-41 Drug Info [526514]
Modulator Carboprost Tromethamine Drug Info [556264]
H2S-releasing latanoprost Drug Info [543781]
NCX-125 Drug Info [543781]
ONO-9054 Drug Info [533184]
PGF2ALPHA-IE Drug Info [533620], [551871]
Tafluprost Drug Info [551871]
Inhibitor LAROPIPRANT Drug Info [528672]
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 523049ClinicalTrials.gov (NCT01126073) Niacin/Laropiprant and Endothelial Function. U.S. National Institutes of Health.
Ref 523270ClinicalTrials.gov (NCT01250587) Dose-Finding Study of PDC31 in Patients With Primary Dysmenorrhea. U.S. National Institutes of Health.
Ref 524354ClinicalTrials.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 530618Mol Endocrinol. 2010 Feb;24(2):436-46. Epub 2010 Jan 5.Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin receptor phosphorylation.
Ref 532003Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81.
Ref 532210Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
Ref 533184IOP-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 533334The effect of prostaglandin F2 alpha-1-isopropylester (PGF2 alpha-IE) on uveoscleral outflow. Prog Clin Biol Res. 1989;312:429-36.
Ref 536361Natural 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 538496FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 017989.
Ref 539256(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 539258(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 540312(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 542110(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 542476(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 551115Clinical pipeline report, company report or official report of Mati therapeutics.
Ref 551493Clinical pipeline report, company report or official report of Pfizer.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 525568AL-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 525673The 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 525721J 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 525853Replacement 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 526505Identification 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 526514THG113: a novel selective FP antagonist that delays preterm labor. Semin Perinatol. 2002 Dec;26(6):389-97.
Ref 528506Preclinical pharmacology of AL-12182, a new ocular hypotensive 11-oxa prostaglandin analog. J Ocul Pharmacol Ther. 2006 Oct;22(5):291-309.
Ref 528672J 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).
Ref 528941Arrest 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 531388Ocular 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 533184IOP-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 533620Role of nitric oxide in PGF2 alpha-induced ocular hyperemia. Exp Eye Res. 1994 Oct;59(4):401-7.
Ref 533982Cloning and expression of a cDNA for the human prostanoid FP receptor. J Biol Chem. 1994 Jan 28;269(4):2632-6.
Ref 534478Ligand 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 537092Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys. J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8.
Ref 537255PGF(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 543781(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 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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