Target Information

Target General Information

Target ID

T75797 (Former ID: TTDS00169)

Target Name

Prostaglandin F2-alpha receptor (PTGFR)

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

Target Type

Successful target

[1]

Disease

[+] 3 Target-related Diseases

Abortion [ICD-11: JA00]

Glaucoma [ICD-11: 9C61]

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

UniProt ID

PF2R_HUMAN

Sequence

MSMNNSKQLVSPAAALLSNTTCQTENRLSVFFSVIFMTVGILSNSLAIAILMKAYQRFRQ
KSKASFLLLASGLVITDFFGHLINGAIAVFVYASDKEWIRFDQSNVLCSIFGICMVFSGL
CPLLLGSVMAIERCIGVTKPIFHSTKITSKHVKMMLSGVCLFAVFIALLPILGHRDYKIQ
ASRTWCFYNTEDIKDWEDRFYLLLFSFLGLLALGVSLLCNAITGITLLRVKFKSQQHRQG
RSHHLEMVIQLLAIMCVSCICWSPFLVTMANIGINGNHSLETCETTLFALRMATWNQILD
PWVYILLRKAVLKNLYKLASQCCGVHVISLHIWELSSIKNSLKVAAISESPVAEKSAST

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3D Structure

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AlphaFold

HIT2.0 ID

T35YGY

Drugs and Modes of Action

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Approved Drug(s)

[+] 7 Approved Drugs

BOL-303259-X

Drug Info

Approved

Open-angle glaucoma

[2]

Carboprost Tromethamine

Drug Info

Approved

Abortion

[3]

Dinoprostone

Drug Info

Approved

Medical abortion

[4], [5]

Latanoprost

Drug Info

Approved

Open-angle glaucoma

[6], [7]

Tafluprost

Drug Info

Approved

Glaucoma/ocular hypertension

[8], [9], [10], [11]

Travoprost

Drug Info

Approved

Open-angle glaucoma

[12], [7]

LAROPIPRANT

Drug Info

Phase 4

Coronary heart disease

[13]

Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

PGF2ALPHA-IE

Drug Info

Phase 3

Glaucoma/ocular hypertension

[14]

ONO-9054

Drug Info

Phase 2

Glaucoma/ocular hypertension

[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 tumour/cancer

[18]

Mode of Action

[+] 4 Modes of Action

Agonist

[+] 16 Agonist drugs

BOL-303259-X

Drug Info

[19]

Latanoprost

Drug Info

[22]

Travoprost

Drug Info

[1]

bimatoprost (free acid form)

Drug Info

[26]

PGF2alpha

Drug Info

[27]

13,14-dihydro-16-m-chlorophenoxy-w-tetranor-PGF1alpha

Drug Info

[28]

AL-8810

Drug Info

[29]

AL12180

Drug Info

[30]

carbacyclin

Drug Info

[32]

cloprostenol

Drug Info

[32]

fluprostenol

Drug Info

[33], [34]

I-BOP

Drug Info

[33]

M&B 28767

Drug Info

[33]

PGD2

Drug Info

[33]

U46619

Drug Info

[32]

[3H]PGF2alpha

Drug Info

[35]

Modulator

[+] 5 Modulator drugs

Carboprost Tromethamine

Drug Info

[20]

Tafluprost

Drug Info

[11]

PGF2ALPHA-IE

Drug Info

[11], [24]

ONO-9054

Drug Info

[15]

NCX-125

Drug Info

[34]

Antagonist

[+] 5 Antagonist drugs

Dinoprostone

Drug Info

[21]

PDC-41

Drug Info

[25]

BUTAPROST

Drug Info

[21]

AS604872

Drug Info

[31]

PDC-31

Drug Info

[34]

Inhibitor

[+] 1 Inhibitor drugs

LAROPIPRANT

Drug Info

[23]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Human Similarity Proteins Human Pathway Affiliation

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Human Similarity Proteins

Human Pathway Affiliation

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
Calcium signaling pathway	hsa04020	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Phospholipase D signaling pathway	hsa04072	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Neuroactive ligand-receptor interaction	hsa04080	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy

Chemical Structure based Activity Landscape of Target

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Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"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

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Co-Targets

Co-Targets Info

Target Poor or Non Binders

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Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 2 KEGG Pathways

Calcium signaling pathway

Neuroactive ligand-receptor interaction

Reactome

[+] 2 Reactome Pathways

Prostanoid ligand receptors

G alpha (q) signalling events

WikiPathways

[+] 7 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

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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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

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

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

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

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

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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