Target Information
| Target General Information | Top | |||||
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| Target ID |
T75797
(Former ID: TTDS00169)
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| Target Name |
Prostaglandin F2-alpha receptor (PTGFR)
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| Synonyms |
Prostanoid FP receptor; PGF2-alpha receptor; PGF2 alpha receptor; PGF receptor; FP prostanoid receptor; FP prostaglandin receptor
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| Gene Name |
PTGFR
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Abortion [ICD-11: JA00] | |||||
| 2 | Glaucoma [ICD-11: 9C61] | |||||
| 3 | Coronary atherosclerosis [ICD-11: BA80] | |||||
| 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).
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MSMNNSKQLVSPAAALLSNTTCQTENRLSVFFSVIFMTVGILSNSLAIAILMKAYQRFRQ
KSKASFLLLASGLVITDFFGHLINGAIAVFVYASDKEWIRFDQSNVLCSIFGICMVFSGL CPLLLGSVMAIERCIGVTKPIFHSTKITSKHVKMMLSGVCLFAVFIALLPILGHRDYKIQ ASRTWCFYNTEDIKDWEDRFYLLLFSFLGLLALGVSLLCNAITGITLLRVKFKSQQHRQG RSHHLEMVIQLLAIMCVSCICWSPFLVTMANIGINGNHSLETCETTLFALRMATWNQILD PWVYILLRKAVLKNLYKLASQCCGVHVISLHIWELSSIKNSLKVAAISESPVAEKSAST Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T35YGY | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 7 Approved Drugs | + | ||||
| 1 | BOL-303259-X | Drug Info | Approved | Open-angle glaucoma | [2] | |
| 2 | Carboprost Tromethamine | Drug Info | Approved | Abortion | [3] | |
| 3 | Dinoprostone | Drug Info | Approved | Medical abortion | [4], [5] | |
| 4 | Latanoprost | Drug Info | Approved | Open-angle glaucoma | [6], [7] | |
| 5 | Tafluprost | Drug Info | Approved | Glaucoma/ocular hypertension | [8], [9], [10], [11] | |
| 6 | Travoprost | Drug Info | Approved | Open-angle glaucoma | [12], [7] | |
| 7 | LAROPIPRANT | Drug Info | Phase 4 | Coronary heart disease | [13] | |
| Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
| 1 | PGF2ALPHA-IE | Drug Info | Phase 3 | Glaucoma/ocular hypertension | [14] | |
| 2 | ONO-9054 | Drug Info | Phase 2 | Glaucoma/ocular hypertension | [15] | |
| 3 | PDC-41 | Drug Info | Phase 1 | Dysmenorrhea | [16] | |
| 4 | bimatoprost (free acid form) | Drug Info | Clinical trial | Alzheimer disease | [17] | |
| 5 | PGF2alpha | Drug Info | Clinical trial | Solid tumour/cancer | [18] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Agonist | [+] 16 Agonist drugs | + | ||||
| 1 | BOL-303259-X | Drug Info | [19] | |||
| 2 | Latanoprost | Drug Info | [22] | |||
| 3 | Travoprost | Drug Info | [1] | |||
| 4 | bimatoprost (free acid form) | Drug Info | [26] | |||
| 5 | PGF2alpha | Drug Info | [27] | |||
| 6 | 13,14-dihydro-16-m-chlorophenoxy-w-tetranor-PGF1alpha | Drug Info | [28] | |||
| 7 | AL-8810 | Drug Info | [29] | |||
| 8 | AL12180 | Drug Info | [30] | |||
| 9 | carbacyclin | Drug Info | [32] | |||
| 10 | cloprostenol | Drug Info | [32] | |||
| 11 | fluprostenol | Drug Info | [33], [34] | |||
| 12 | I-BOP | Drug Info | [33] | |||
| 13 | M&B 28767 | Drug Info | [33] | |||
| 14 | PGD2 | Drug Info | [33] | |||
| 15 | U46619 | Drug Info | [32] | |||
| 16 | [3H]PGF2alpha | Drug Info | [35] | |||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | Carboprost Tromethamine | Drug Info | [20] | |||
| 2 | Tafluprost | Drug Info | [11] | |||
| 3 | PGF2ALPHA-IE | Drug Info | [11], [24] | |||
| 4 | ONO-9054 | Drug Info | [15] | |||
| 5 | NCX-125 | Drug Info | [34] | |||
| Antagonist | [+] 5 Antagonist drugs | + | ||||
| 1 | Dinoprostone | Drug Info | [21] | |||
| 2 | PDC-41 | Drug Info | [25] | |||
| 3 | BUTAPROST | Drug Info | [21] | |||
| 4 | AS604872 | Drug Info | [31] | |||
| 5 | PDC-31 | Drug Info | [34] | |||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | LAROPIPRANT | Drug Info | [23] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Calcium signaling pathway | |||||
| 2 | Neuroactive ligand-receptor interaction | |||||
| Reactome | [+] 2 Reactome Pathways | + | ||||
| 1 | Prostanoid ligand receptors | |||||
| 2 | G alpha (q) signalling events | |||||
| WikiPathways | [+] 7 WikiPathways | + | ||||
| 1 | Prostaglandin Synthesis and Regulation | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| 3 | Gastrin-CREB signalling pathway via PKC and MAPK | |||||
| 4 | Small Ligand GPCRs | |||||
| 5 | GPCR ligand binding | |||||
| 6 | GPCR downstream signaling | |||||
| 7 | GPCRs, Other | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Prostaglandin subtype-selective and non-selective IOP-lowering comparison in monkeys. J Ocul Pharmacol Ther. 2009 Feb;25(1):1-8. | |||||
| REF 2 | Evaluation of the Effect of Latanoprostene Bunod Ophthalmic Solution, 0.024% in Lowering Intraocular Pressure over 24 in Healthy Japanese Subjects.Adv Ther. 2015 Nov;32(11):1128-39. | |||||
| REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 017989. | |||||
| REF 4 | 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. (Ligand id: 1916). | |||||
| REF 5 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 020411. | |||||
| REF 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. (Ligand id: 1961). | |||||
| REF 7 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 8 | 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. (Ligand id: 7451). | |||||
| REF 9 | Nat Rev Drug Discov. 2013 Feb;12(2):87-90. | |||||
| REF 10 | Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin receptor phosphorylation. Mol Endocrinol. 2010 Feb;24(2):436-46. | |||||
| REF 11 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 12 | 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. (Ligand id: 7102). | |||||
| REF 13 | ClinicalTrials.gov (NCT01126073) A Double Blind, Randomized Study to Compare Influence of Niacin/Laropiprant on Functional and Morphological Characteristics of Arterial Wall and Parameters of Inflammation in Subjects With Coronary Heart Disease Already Treated With a Statin in Miran Sebestjen, University Medical Centre Ljubljana. | |||||
| REF 14 | The effect of prostaglandin F2 alpha-1-isopropylester (PGF2 alpha-IE) on uveoscleral outflow. Prog Clin Biol Res. 1989;312:429-36. | |||||
| REF 15 | 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. | |||||
| REF 16 | ClinicalTrials.gov (NCT01250587) Dose-Finding Study of PDC31 in Patients With Primary Dysmenorrhea. U.S. National Institutes of Health. | |||||
| REF 17 | 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. (Ligand id: 1959). | |||||
| REF 18 | Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81. | |||||
| REF 19 | 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. | |||||
| REF 20 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 21 | 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. | |||||
| REF 22 | PGF(2alpha) FP receptor contributes to brain damage following transient focal brain ischemia. Neurotox Res. 2009 Jan;15(1):62-70. | |||||
| REF 23 | 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. | |||||
| REF 24 | Role of nitric oxide in PGF2 alpha-induced ocular hyperemia. Exp Eye Res. 1994 Oct;59(4):401-7. | |||||
| REF 25 | THG113: a novel selective FP antagonist that delays preterm labor. Semin Perinatol. 2002 Dec;26(6):389-97. | |||||
| REF 26 | 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. | |||||
| REF 27 | 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. | |||||
| REF 28 | 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. | |||||
| REF 29 | 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. | |||||
| REF 30 | Preclinical pharmacology of AL-12182, a new ocular hypotensive 11-oxa prostaglandin analog. J Ocul Pharmacol Ther. 2006 Oct;22(5):291-309. | |||||
| REF 31 | 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. | |||||
| REF 32 | 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. | |||||
| REF 33 | 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. | |||||
| REF 34 | 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). | |||||
| REF 35 | Cloning and expression of a cDNA for the human prostanoid FP receptor. J Biol Chem. 1994 Jan 28;269(4):2632-6. | |||||
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