Target Information

Target General Information

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Target ID

T68782 (Former ID: TTDR00802)

Target Name

Prostaglandin D2 receptor (PTGDR)

Synonyms

Prostanoid DP receptor; PGD2 receptor; PGD receptor

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Gene Name

PTGDR

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Coronary atherosclerosis [ICD-11: BA80]

Function

The activity of this receptor is mainly mediated by G(s) proteins that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP. A mobilization of calcium is also observed, but without formation of inositol 1,4,5-trisphosphate. Receptor for prostaglandin D2 (PGD2).

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BioChemical Class

GPCR rhodopsin

UniProt ID

PD2R_HUMAN

Sequence

MKSPFYRCQNTTSVEKGNSAVMGGVLFSTGLLGNLLALGLLARSGLGWCSRRPLRPLPSV
FYMLVCGLTVTDLLGKCLLSPVVLAAYAQNRSLRVLAPALDNSLCQAFAFFMSFFGLSST
LQLLAMALECWLSLGHPFFYRRHITLRLGALVAPVVSAFSLAFCALPFMGFGKFVQYCPG
TWCFIQMVHEEGSLSVLGYSVLYSSLMALLVLATVLCNLGAMRNLYAMHRRLQRHPRSCT
RDCAEPRADGREASPQPLEELDHLLLLALMTVLFTMCSLPVIYRAYYGAFKDVKEKNRTS
EEAEDLRALRFLSVISIVDPWIFIIFRSPVFRIFFHKIFIRPLRYRSRCSNSTNMESSL

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Approved Drug(s)

[+] 1 Approved Drugs

LAROPIPRANT

Drug Info

Phase 4

Coronary heart disease

[2]

Clinical Trial Drug(s)

[+] 11 Clinical Trial Drugs

QAW-039

Drug Info

Phase 3

Asthma

[3]

Setipiprant

Drug Info

Phase 3

Asthma

[4]

AMG 853

Drug Info

Phase 2

Asthma

[5]

MK-1029

Drug Info

Phase 2

Asthma

[6]

ONO-4053

Drug Info

Phase 2

Allergic rhinitis

[7]

S-555739

Drug Info

Phase 2

Allergy

[8]

TS-022

Drug Info

Phase 2

Atopic dermatitis

[9]

192C86

Drug Info

Phase 1

Thrombosis

[10]

MK-1092

Drug Info

Phase 1

Type-1 diabetes

[11]

SAR-389644

Drug Info

Phase 1

Allergic rhinitis

[12]

PGF2alpha

Drug Info

Clinical trial

Solid tumour/cancer

[13]

Discontinued Drug(s)

[+] 4 Discontinued Drugs

Laropiprant+niacin

Drug Info

Discontinued in Phase 3

Dyslipidemia

[14]

S-5751

Drug Info

Discontinued in Phase 2

Rhinitis

[15], [16]

ONO-4127

Drug Info

Discontinued in Phase 1

Allergic rhinitis

[17]

ZK-118182

Drug Info

Terminated

Thrombosis

[18], [19]

Mode of Action

[+] 4 Modes of Action

Inhibitor

[+] 3 Inhibitor drugs

LAROPIPRANT

Drug Info

[1]

MK-1029

Drug Info

[23]

DIASTEREOMER 2

Drug Info

[1]

Antagonist

[+] 12 Antagonist drugs

QAW-039

Drug Info

[20]

Setipiprant

Drug Info

[21]

ONO-4053

Drug Info

[24]

S-555739

Drug Info

[8]

MK-1092

Drug Info

[27]

SAR-389644

Drug Info

[28]

Laropiprant+niacin

Drug Info

[30]

S-5751

Drug Info

[31]

ONO-4127

Drug Info

[32]

AH6809

Drug Info

[29]

BWA868C

Drug Info

[34], [36]

ONO-AE3-237

Drug Info

[39]

Modulator

[+] 4 Modulator drugs

AMG 853

Drug Info

[22]

192C86

Drug Info

[26]

ZK-118182

Drug Info

[33]

TTH 03-001

Drug Info

[42]

Agonist

[+] 16 Agonist drugs

TS-022

Drug Info

[25]

PGF2alpha

Drug Info

[29]

15-deoxy-Delta12,14-PGJ2

Drug Info

[34]

butaprost (free acid form)

Drug Info

[29]

BW 245C

Drug Info

[35]

carbacyclin

Drug Info

[29]

cloprostenol

Drug Info

[29]

Delta12-PGJ2

Drug Info

[34]

L-644,698

Drug Info

[37]

L-888,291

Drug Info

[38]

PGD2

Drug Info

[37], [40]

PGJ2

Drug Info

[34]

RS 93520

Drug Info

[41]

SQ-27986

Drug Info

[41]

U46619

Drug Info

[29]

ZK110841

Drug Info

[34]

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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Olfactory receptor 10H3 (OR10H3)	PF13853	25.455 (28/110)	2.00E-03
Olfactory receptor 10H5 (OR10H5)	PF13853	27.211 (40/147)	3.00E-03

KEGG Pathway	Pathway ID	Affiliated Target	Pathway Map
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 Regulators

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Target-interacting Proteins

Target-interacting Proteins 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

[+] 1 KEGG Pathways

Neuroactive ligand-receptor interaction

Pathwhiz Pathway

[+] 1 Pathwhiz Pathways

Intracellular Signalling Through PGD2 receptor and Prostaglandin D2

PID Pathway

[+] 1 PID Pathways

Thromboxane A2 receptor signaling

Reactome

[+] 2 Reactome Pathways

Prostanoid ligand receptors

G alpha (s) signalling events

WikiPathways

[+] 5 WikiPathways

Prostaglandin Synthesis and Regulation

GPCRs, Class A Rhodopsin-like

Small Ligand GPCRs

GPCR ligand binding

GPCR downstream signaling

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

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 2

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 3

ClinicalTrials.gov (NCT02563067) Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.

REF 4

ClinicalTrials.gov (NCT01484119) Efficacy, Safety, and Tolerability Study of ACT-129968 in Patients With Seasonal Allergic Rhinitis. U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT01018550) AMG 853 Phase 2 Study in Subjects With Inadequately Controlled Asthma. U.S. National Institutes of Health.

REF 6

ClinicalTrials.gov (NCT01624974) Study to Evaluate the Effectiveness and Safety of MK-1029 in the Treatment of Persistent Asthma That is Not Controlled With Montelukast (ML) in Adults (MK-1029-011 AM2). U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT01748344) Phase II Study Evaluating ONO-4053 and Cetirizine in Subjects With Seasonal Allergic Rhinitis. U.S. National Institutes of Health.

REF 8

Clinical pipeline report, company report or official report of Shionogi (2011).

REF 9

ClinicalTrials.gov (NCT00914186) Study of TS-022 in Adult Patients With Atopic Dermatitis With Pruritus (POC). U.S. National Institutes of Health.

REF 10

The effect of a prostaglandin DP-receptor partial agonist (192C86) on platelet aggregation and the cardiovascular system in healthy volunteers. Br J Clin Pharmacol. 1992 Oct;34(4):344-51.

REF 11

ClinicalTrials.gov (NCT03170544) Single Ascending Dose Study of MK-1092 in Healthy Participants and in Participants With Type 1 and Type 2 Diabetes Mellitus (MK-1092-001). U.S. National Institutes of Health.

REF 12

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025865)

REF 13

Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81.

REF 14

ClinicalTrials.gov (NCT01054508) Effect of Tredaptive on Serum Lipoproteins and Inflammatory Markers. U.S. National Institutes of Health.

REF 15

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: 1898).

REF 16

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012090)

REF 17

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018932)

REF 18

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003331)

REF 20

Effect Of QAW039, An Oral Prostaglandin D2 Receptor (DP2/CRTh2) Antagonist, Upon Sputum And Bronchial Eosinophilic Inflammation And Clinical Outcomes In Treatment-Resistant Asthma: A Phase 2a Randomized Placebo-Controlled Trial. American Thoracic Society Journals. 2015.

REF 21

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 22

Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients.J Allergy Clin Immunol.2013 Feb;131(2):339-45.

REF 23

Update on the status of DP2 receptor antagonists; from proof of concept through clinical failures to promising new drugs. Expert Opin Investig Drugs. 2014 Jan;23(1):55-66.

REF 24

Effect of ONO-4053, a DP1 (prostaglandin D2 receptor) Antagonist, on Prostaglandin D2-Induced Nasal Congestion. Journal of Allergy and Clinical Immunology Volume 135, Issue 2, Supplement, February 2015, Pages AB219.

REF 25

Effects of TS-022, a newly developed prostanoid DP1 receptor agonist, on experimental pruritus, cutaneous barrier disruptions and atopic dermatitis... Eur J Pharmacol. 2007 Feb 5;556(1-3):207-14.

REF 26

Prostanoid receptor antagonists: development strategies and therapeutic applications. Br J Pharmacol. 2009 September; 158(1): 104-145.

REF 27

The challenge of modulating -cell autoimmunity in type 1 diabetes. Lancet Diabetes Endocrinol. 2019 Jan;7(1):52-64.

REF 28

US patent application no. 2008,0300,217, Combination therapy with fumaric acid esters for the treatment of autoimmune and,or inflammatory disorders.

REF 29

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 30

Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.

REF 31

Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.

REF 32

Sleep-wake regulation by prostaglandin D2 and adenosine. Brain Nerve. 2012 Jun;64(6):621-8.

REF 33

Characterization of prostanoid receptors mediating inhibition of histamine release from anti-IgE-activated rat peritoneal mast cells. Br J Pharmacol. 2000 Feb;129(3):589-97.

REF 34

Characterization of the recombinant human prostanoid DP receptor and identification of L-644,698, a novel selective DP agonist. Br J Pharmacol. 1998 Apr;123(7):1317-24.

REF 35

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 36

Pharmacology and autoradiography of human DP prostanoid receptors using [(3)H]-BWA868C, a DP receptor-selective antagonist radioligand. Br J Pharmacol. 2000 Nov;131(6):1025-38.

REF 37

A novel biological role for prostaglandin D2 is suggested by distribution studies of the rat DP prostanoid receptor. Eur J Pharmacol. 1999 Jul 14;377(1):101-15.

REF 38

Identification of a potent and selective synthetic agonist at the CRTH2 receptor. Mol Pharmacol. 2005 Jun;67(6):1834-9.

REF 39

Prostaglandin D2 inhibits the production of IFN-gamma by invariant NK T cells: consequences in the control of B16 melanoma. J Immunol. 2008 Jan 15;180(2):783-92.

REF 40

GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid EP4 receptor antagonist. Br J Pharmacol. 2006 Jun;148(3):326-39.

REF 41

Affinities, selectivities, potencies, and intrinsic activities of natural and synthetic prostanoids using endogenous receptors: focus on DP class prostanoids. J Pharmacol Exp Ther. 2000 May;293(2):321-8.

REF 42

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