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DP2 receptor

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 339

Nomenclature: DP2 receptor

Family: Prostanoid receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 395 11q12.2 PTGDR2 prostaglandin D2 receptor 2 27
Mouse 7 382 19 A Ptgdr2 prostaglandin D2 receptor 2 1,15
Rat 7 403 1q43 Ptgdr2 prostaglandin D2 receptor 2 33
Previous and Unofficial Names Click here for help
CRTH2 [31] | CD294 | G protein-coupled receptor 44 | prostaglandin D2 receptor 2 | PGD2 receptor | Gpr44
Database Links Click here for help
Specialist databases
GPCRdb pd2r2_human (Hs), pd2r2_mouse (Mm), pd2r2_rat (Rn)
Other databases
Alphafold Q9Y5Y4 (Hs), Q9Z2J6 (Mm), Q6XKD3 (Rn)
ChEMBL Target CHEMBL5071 (Hs), CHEMBL2291 (Mm), CHEMBL1075112 (Rn)
Ensembl Gene ENSG00000183134 (Hs), ENSMUSG00000034117 (Mm), ENSRNOG00000036631 (Rn)
Entrez Gene 11251 (Hs), 14764 (Mm), 309212 (Rn)
Human Protein Atlas ENSG00000183134 (Hs)
KEGG Gene hsa:11251 (Hs), mmu:14764 (Mm), rno:309212 (Rn)
OMIM 604837 (Hs)
Pharos Q9Y5Y4 (Hs)
RefSeq Nucleotide NM_004778 (Hs), NM_009962 (Mm), NM_001012070 (Rn)
RefSeq Protein NP_004769 (Hs), NP_034092 (Mm), NP_001012070 (Rn)
UniProtKB Q9Y5Y4 (Hs), Q9Z2J6 (Mm), Q6XKD3 (Rn)
Wikipedia PTGDR2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human DP2 receptor with antagonist, fevipiprant
PDB Id:  6D26
Ligand:  fevipiprant
Resolution:  2.798Å
Species:  Human
References:  40
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human DP2 receptor with antagonist, CAY10471 (a.k.a. TM30089)
PDB Id:  6D27
Ligand:  TM30089
Resolution:  2.738Å
Species:  Human
References:  40
Natural/Endogenous Ligands Click here for help
PGD3
PGD2
PGE2
PGF2α
PGI2
PGJ2
Comments: 11-Dehydro-thromboxane B2, a breakdown product of thromboxane A2 is an additional endogenous agonist of this receptor
Potency order of endogenous ligands
PGD2 >> PGF2α, PGE2 > PGI2, thromboxane A2

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]PGD2 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Full agonist 7.8 – 8.2 pKd 23,33
⤷ pKd 7.8 – 8.2 (Kd 1.6x10-8 – 6x10-9 M) [23,33]
[3H]PGD2 Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Full agonist 8.0 pKd 33
⤷ pKd 8.0 [33]
L-888,607 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 9.1 pKi 12
⤷ pKi 9.1 (Ki 8x10-10 M) [12]
15(R)-15-methyl-PGD2 Small molecule or natural product Ligand has a PDB structure Hs Full agonist 8.9 pKi 15,25,36
⤷ pKi 8.9 [15,25,36]
15-deoxy-Δ12,14-PGJ2 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.5 pKi 31
⤷ pKi 8.5 [31]
Δ12-PGJ2 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.2 pKi 31
⤷ pKi 8.2 [31]
PGJ2 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 8.2 pKi 31
⤷ pKi 8.2 [31]
PGD2 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 7.6 – 8.6 pKi 31,36
⤷ pKi 7.6 – 8.6 [31,36]
13,14-dihydro-15-keto-PGD2 Small molecule or natural product Hs Full agonist 7.4 – 8.5 pKi 15,31,36
⤷ pKi 7.4 – 8.5 (Ki 3.98x10-8 – 3.16x10-9 M) [15,31,36]
15-deoxy-Δ12,14-PGJ2 Small molecule or natural product Mm Full agonist 7.6 pKi 15
⤷ pKi 7.6 [15]
13,14-dihydro-15-keto-PGD2 Small molecule or natural product Mm Full agonist 7.5 – 7.7 pKi 14-15
⤷ pKi 7.5 – 7.7 [14-15]
15(S)-15-methyl-PGD2 Small molecule or natural product Hs Full agonist 7.5 pKi 31
⤷ pKi 7.5 [31]
PGD2 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Mm Full agonist 7.4 – 7.5 pKi 14-15
⤷ pKi 7.4 – 7.5 [14-15]
PGD3 Small molecule or natural product Ligand is endogenous in the given species Mm Full agonist 7.4 pKi 15
⤷ pKi 7.4 [15]
L-888,291 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.3 pKi 12
⤷ pKi 7.3 (Ki 4.8x10-8 M) [12]
PGJ2 Small molecule or natural product Ligand is endogenous in the given species Mm Full agonist 7.3 pKi 15
⤷ pKi 7.3 [15]
15-deoxy-Δ12,14-PGD2 Small molecule or natural product Mm Full agonist 7.3 pKi 15
⤷ pKi 7.3 [15]
indomethacin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 6.1 – 7.7 pKi 31,36
⤷ pKi 6.1 – 7.7 [31,36]
Δ12-PGJ2 Small molecule or natural product Mm Full agonist 6.4 pKi 15
⤷ pKi 6.4 [15]
PGF2α Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 6.4 pKi 31
⤷ pKi 6.4 [31]
13,14-dihydro-15-keto-PGF2α Small molecule or natural product Hs Full agonist 6.3 pKi 31
⤷ pKi 6.3 [31]
PGF2α Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Mm Full agonist 6.2 pKi 15
⤷ pKi 6.2 [15]
indomethacin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Mm Full agonist 5.7 – 6.0 pKi 14-15
⤷ pKi 5.7 – 6.0 [14-15]
PGE2 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Mm Full agonist 5.5 pKi 15
⤷ pKi 5.5 [15]
U46619 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 5.5 pKi 31
⤷ pKi 5.5 [31]
PGE2 Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 5.3 pKi 31
⤷ pKi 5.3 [31]
PGD2 Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 8.2 pIC50 33
⤷ pIC50 8.2 [33]
View species-specific agonist tables
Agonist Comments
13,14-dihydro-15-oxo-PGD2 and 15R-15-methyl-PGD2 are selective DP2 agonists [15,25]. The COX-1/2 inhibitor indomethacin [16] and the thromboxane metabolite 11-dehydro TXB2 [6] are low-potency DP2 agonists.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
fevipiprant Small molecule or natural product Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Antagonist 9.0 pKd 37-38
⤷ pKd 9.0 (Kd 1.02x10-9 M) [37-38]
[3H]ramatroban Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Hs Antagonist 8.1 pKd 36
⤷ pKd 8.1 [36]
QAV680 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Antagonist 7.8 pKd 37
⤷ pKd 7.8 (Kd 1.51x10-8 M) [37]
TM30089 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 9.2 pKi 39
⤷ pKi 9.2 (Ki 6x10-10 M) [39]
timapiprant Small molecule or natural product Immunopharmacology Ligand Rn Antagonist 8.5 pKi 28
⤷ pKi 8.5 (Ki 3x10-9 M) [28]
Description: Displacement of [3H]PGD2 from rat recombinant DP2
compound 51 [Crosignani et al., 2011] Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.2 pKi 8
⤷ pKi 8.2 (Ki 6.9x10-9 M) [8]
timapiprant Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Antagonist 7.9 pKi 28
⤷ pKi 7.9 (Ki 1.3x10-8 M) [28]
Description: Displacement of [3H]PGD2 from human recombinant DP2
ramatroban Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 7.4 pKi 36
⤷ pKi 7.4 [36]
ramatroban Small molecule or natural product Ligand has a PDB structure Mm Antagonist 7.3 pKi 14
⤷ pKi 7.3 [14]
ARRY-502 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 7.6 pEC50 5
⤷ pEC50 7.6 (EC50 2.56x10-8 M) [5]
Description: Membrane binding assay using human DP2 stably expressed in K562 leukemia cells.
TM30089 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 8.9 pIC50 29,39
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [29,39]
vidupiprant Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Antagonist 8.5 pIC50 20
⤷ pIC50 8.5 (IC50 3x10-9 M) [20]
AZD1981 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Antagonist 8.4 pIC50 21
⤷ pIC50 8.4 (IC50 4.3x10-9 M) [21]
Description: Displacement of [3H]PGD2 from human DP2 receptor
AM-461 Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 8.3 pIC50 4
⤷ pIC50 8.3 (IC50 5.2x10-9 M) [4]
Description: Radioligand ([3H]PGD2) displacement from human DP2 receptors expressed in HEK293 cells.
setipiprant Small molecule or natural product Immunopharmacology Ligand Hs Antagonist 8.2 pIC50 9
⤷ pIC50 8.2 (IC50 6x10-9 M) [9]
AM-461 Small molecule or natural product Immunopharmacology Ligand Rn Antagonist 8.1 pIC50 4
⤷ pIC50 8.1 (IC50 7x10-9 M) [4]
Description: Radioligand ([3H]PGD2) displacement from rat DP2 receptors.
AM-461 Small molecule or natural product Immunopharmacology Ligand Mm Antagonist 8.0 pIC50 4
⤷ pIC50 8.0 (IC50 9.7x10-9 M) [4]
Description: Radioligand ([3H]PGD2) displacement from mouse DP2 receptor.
ramatroban Small molecule or natural product Ligand has a PDB structure Rn Antagonist 7.3 pIC50 33
⤷ pIC50 7.3 [33]
View species-specific antagonist tables
Antagonist Comments
The TP receptor antagonist ramatroban also blocks the DP2 receptor [35].
For a review on the use of DP2 antagonists to treat allergic inflammation see [22].
OC000459 antagonises [3H]PGD2 binding to native DP2 receptors in human Th2 lymphocytes with a Ki of 4nM [28].
ACT-453859 (structure not disclosed) is a clinical candidate DP2 receptor antagonist for allergic inflammation, predominantly for asthma [13,19,34].
AZD1981 is a selective DP2 receptor antagonist trialled for the treatment of allergic asthma [3].
DP2 antagonist TM30089 suppresses PGD2-dependent human ILC2 cell migration and cytokine production [43].
Immunopharmacology Comments
The DP2 receptor (a.k.a. CRTH2, chemoattractant receptor-homologous molecule expressed on T-helper 2 cells) is expressed exclusively by a range of human immune cells including Th2 cells, basophils, eosinophils and innate lymphoid cells [17,26]. It mediates the proinflammatory effects of mast cell-derived prostaglandin D2 (PGD2) [26]. The DP2/PGD2 axis regulates the activation and chemotaxis of DP2 receptor +ve cells, and downstream pro-inflammatory events including stimulation of Th2 cytokine synthesis, local vasodilation and edema. Eosinophil morphology changes are promoted by PGD2-induced DP2 activation, as is enhanced migration from the bone marrow. Eosinophil degranulation and chemotactic responsiveness are also enhanced by this pathway. DP2-expressing type 2 innate lymphoid cells (ILC2) respond to and migrate toward PGD2 in vitro. Mice deficient in Ptgdr2 exhibited reduced ILC2 responses and inflammation in a murine model of helminth-induced pulmonary type 2 inflammation [41].

In human lung tissue specimens both DP1 and DP2 receptors are detected on alveolar macrophages, and activation of these two receptors aggravates airway neutrophilia in a mouse model [18].

Selective DP2 receptor antagonists are being actively sought as anti-inflammatory agents. AZD1981 has recently been trialled in a large multi-centred Phase 2b study (n=1,140 patients) for the novel treatment of allergic asthma [3], GB001/ADC3680B (Gossamer Bio, no structure disclosed) is also in Phase 2 for asthma [2], and fevipiprant has advanced to Phase 3 evaluation for asthma and other inflammatory airway conditions. Several more antagonists have demonstrated efficacy in animal models of inflammatory diseases.
Cell Type Associations
Immuno Cell Type:  T cells
Cell Ontology Term:   T-helper 2 cell (CL:0000546)
Comment:  Expression of the DP2 receptor is restricted to eosinophils, basophils, Th2 cells, and innate lymphoid cells.
References:  17
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   basophil (CL:0000767)
eosinophil (CL:0000771)
Comment:  Expression of the DP2 receptor is restricted to eosinophils, basophils, Th2 cells, and innate lymphoid cells.
References:  17,24
Immuno Cell Type:  Innate lymphoid cells
Cell Ontology Term:   innate lymphoid cell (CL:0001065)
Comment:  Expression of the DP2 receptor is restricted to eosinophils, basophils, Th2 cells, and innate lymphoid cells.
References:  24
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
References:  15,31
Tissue Distribution Click here for help
Eosinophils.
Species:  Human
Technique:  RT-PCR, Southern blotting and in situ hybridisation.
References:  11
Stomach, small intestine, heart, thymus > colon, spinal cord, peripheral blood > brain, skeletal muscle, spleen.
Species:  Human
Technique:  Northern blotting.
References:  31
Eosinophils.
Species:  Human
Technique:  in situ hybridisation.
References:  31
Th2-type lymphocytes.
Species:  Human
Technique:  Northern blotting.
References:  27
Liver, lung, kidney, brain, heart, thymus, spleen, Th1 and Th2 cells.
Species:  Mouse
Technique:  RT-PCR.
References:  1
Lung, brain, ovary, spleen.
Species:  Rat
Technique:  RT-PCR.
References:  33
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of Ca2+ levels in L1.2 cells transfected with the rat DP2 receptor.
Species:  Rat
Tissue:  L1.2 cells.
Response measured:  Ca2+ mobilisation.
References:  33
Measurement of Ca2+ levels in L1.2 cells transfected with the mouse DP2 receptor.
Species:  Mouse
Tissue:  L1.2 cells.
Response measured:  Ca2+ mobilisation.
References:  33
Measurement of cAMP levels in HEK 293 cells transfected with the human DP2 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  31
Measurement of cAMP levels in ER293 cells transfected with the mouse DP2 receptor.
Species:  Mouse
Tissue:  ER293 cells.
Response measured:  Inhibition of cAMP accumulation.
References:  15
Measurement of cell migration of ER293 cells transfected with the mouse DP2 receptor.
Species:  Mouse
Tissue:  ER293 cells.
Response measured:  Induction of chemotaxis via a PI3 kinase-dependent pathway.
References:  15
Measurement of Ca2+ levels in K562 cells transfected with the human DP2 receptor.
Species:  Human
Tissue:  K562 cells.
Response measured:  Ca2+ mobilisation.
References:  16
Measurement of Ca2+ mobilisation in human Th2 cells endogenously expressing the DP2 receptor.
Species:  Human
Tissue:  Th2 cells.
Response measured:  Ca2+ mobilisation.
References:  10,16
Measurement of cell migration of Jurkat cells transfected with the human DP2 receptor.
Species:  Human
Tissue:  Jurkat cells.
Response measured:  Induction of chemotaxis.
References:  16
Measurement of cell migration of human Th2 cells, basophils and eosinophils endogenously expressing the DP2 receptor. Induction of mobilisation has also been reported in Guinea pig eosinophils.
Species:  Human
Tissue:  Th2 cells, basophils, eosinophils.
Response measured:  Induction of chemotaxis.
References:  16,32
Measurement of CD11b upregulation in human eosinophils endogenously expressing the human DP2 receptor.
Species:  Human
Tissue:  Eosinophils.
Response measured:  CD11b upregulation.
References:  32
Measurement of shape change of human basophils and eosinophils endogenously expressing the human DP2 receptor. This effect has also been noted in eosinophils from dogs and Guinea pigs.
Species:  Human
Tissue:  Basophils and eosinophils.
Response measured:  Shape change.
References:  32
Physiological Functions Click here for help
Eosinophil activation, chemotaxis and degranulation.
Species:  Human
Tissue:  Eosinophils.
References:  11
Stimulation of cytokine production.
Species:  Human
Tissue:  Th2 cells.
References:  42
Eosinophil activation.
Species:  Human
Tissue:  Eosinophils.
References:  10
Physiological Functions Comments
DP2-mediated activation has been reported in canine granulocytes [32].
Physiological Consequences of Altering Gene Expression Click here for help
In an allergic inflammatory model of asthma, DP2 knockout mice show enhanced eosinophil recruitment into the lung compared with wild-type littermates.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  7
DP2 receptor knockout mice exhibit decreased cutaneous inflammatory responses. Reduced lymphocyte, eosinophil and basophil infiltration is observed along with a decrease in RANTES production.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  30
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44		 MGI:1330275  MP:0008721 abnormal chemokine level PMID: 16888024 
Gpr44tm1Byl Gpr44tm1Byl/Gpr44tm1Byl
involves: C57BL/6J		 MGI:1330275  MP:0003009 abnormal cytokine secretion PMID: 16081770 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44		 MGI:1330275  MP:0001845 abnormal inflammatory response PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44		 MGI:1330275  MP:0002492 decreased IgE level PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44		 MGI:1330275  MP:0001876 decreased inflammatory response PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44		 MGI:1330275  MP:0009815 decreased prostaglandin level PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
C.129-Gpr44		 MGI:1330275  MP:0005616 decreased susceptibility to type IV hypersensitivity reaction PMID: 16888024 
Gpr44tm1Tasa Gpr44tm1Tasa/Gpr44tm1Tasa
involves: 129/Sv * BALB/c		 MGI:1330275  MP:0008723 impaired eosinophil recruitment PMID: 18097056 
Gpr44tm1Byl Gpr44tm1Byl/Gpr44tm1Byl
involves: C57BL/6J		 MGI:1330275  MP:0005011 increased eosinophil cell number PMID: 16081770 

References

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1. Abe H, Takeshita T, Nagata K, Arita T, Endo Y, Fujita T, Takayama H, Kubo M, Sugamura K. (1999) Molecular cloning, chromosome mapping and characterization of the mouse CRTH2 gene, a putative member of the leukocyte chemoattractant receptor family. Gene, 227 (1): 71-7. [PMID:9931443]

2. Asano K, Sagara H, Ichinose M, Hirata M, Nakajima A, Ortega H, Tohda Y. (2020) A Phase 2a Study of DP2 Antagonist GB001 for Asthma. J Allergy Clin Immunol Pract, 8 (4): 1275-1283.e1. [PMID:31778823]

3. Bateman ED, O'Brien C, Rugman P, Luke S, Ivanov S, Uddin M. (2018) Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting β2-agonists in patients with atopic asthma. Drug Des Devel Ther, 12: 1093-1106. [PMID:29765200]

4. Brittan JE, King CD, Stearns BA. (2011) DP2 ANTAGONIST AND USES THEREOF. Patent number: WO2011085033. Assignee: PANMIRA PHARMACEUTICALS. Priority date: 06/01/2010. Publication date: 14/07/2011.

5. Burgess LE, Clark CT, Cook A, Corrette CP, Delise RK, Doherty GA, Hunt KW, Romoff T. (2009) 6-substituted phenoxychroman carboxylic acid derivatives. Patent number: WO2009158426A1. Assignee: Array Biopharma Inc.. Priority date: 25/06/2008. Publication date: 30/12/2009.

6. Böhm E, Sturm GJ, Weiglhofer I, Sandig H, Shichijo M, McNamee A, Pease JE, Kollroser M, Peskar BA, Heinemann A. (2004) 11-Dehydro-thromboxane B2, a stable thromboxane metabolite, is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and basophils. J Biol Chem, 279 (9): 7663-70. [PMID:14668348]

7. Chevalier E, Stock J, Fisher T, Dupont M, Fric M, Fargeau H, Leport M, Soler S, Fabien S, Pruniaux MP et al.. (2005) Cutting edge: chemoattractant receptor-homologous molecule expressed on Th2 cells plays a restricting role on IL-5 production and eosinophil recruitment. J Immunol, 175 (4): 2056-60. [PMID:16081770]

8. Crosignani S, Jorand-Lebrun C, Campbell G, Prêtre A, Grippi-Vallotton T, Quattropani A, Bouscary-Desforges G, Bombrun A, Missotten M, Humbert Y et al.. (2011) Discovery of a Novel Series of CRTH2 (DP2) Receptor Antagonists Devoid of Carboxylic Acids. ACS Med Chem Lett, 2 (12): 938-42. [PMID:24900284]

9. Fretz H, Valdenaire A, Pothier J, Hilpert K, Gnerre C, Peter O, Leroy X, Riederer MA. (2013) Identification of 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (setipiprant/ACT-129968), a potent, selective, and orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist. J Med Chem, 56 (12): 4899-911. [PMID:23721423]

10. Gazi L, Gyles S, Rose J, Lees S, Allan C, Xue L, Jassal R, Speight G, Gamble V, Pettipher R. (2005) Delta12-prostaglandin D2 is a potent and selective CRTH2 receptor agonist and causes activation of human eosinophils and Th2 lymphocytes. Prostaglandins Other Lipid Mediat, 75 (1-4): 153-67. [PMID:15789622]

11. Gervais FG, Cruz RP, Chateauneuf A, Gale S, Sawyer N, Nantel F, Metters KM, O'neill GP. (2001) Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP. J Allergy Clin Immunol, 108 (6): 982-8. [PMID:11742277]

12. Gervais FG, Morello JP, Beaulieu C, Sawyer N, Denis D, Greig G, Malebranche AD, O'Neill GP. (2005) Identification of a potent and selective synthetic agonist at the CRTH2 receptor. Mol Pharmacol, 67 (6): 1834-9. [PMID:15755909]

13. Géhin M, Strasser DS, Zisowsky J, Farine H, Groenen PM, Dingemanse J, Sidharta PN. (2015) A novel CRTH2 antagonist: Single- and multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-453859 in healthy subjects. J Clin Pharmacol, 55 (7): 787-97. [PMID:25655470]

14. Hata AN, Lybrand TP, Breyer RM. (2005) Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. J Biol Chem, 280: 32442-32451. [PMID:16030019]

15. Hata AN, Zent R, Breyer MD, Breyer RM. (2003) Expression and molecular pharmacology of the mouse CRTH2 receptor. J Pharmacol Exp Ther, 306 (2): 463-70. [PMID:12721327]

16. Hirai H, Tanaka K, Takano S, Ichimasa M, Nakamura M, Nagata K. (2002) Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2. J Immunol, 168 (3): 981-5. [PMID:11801628]

17. Hirai H, Tanaka K, Yoshie O, Ogawa K, Kenmotsu K, Takamori Y, Ichimasa M, Sugamura K, Nakamura M, Takano S et al.. (2001) Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med, 193 (2): 255-61. [PMID:11208866]

18. Jandl K, Stacher E, Bálint Z, Sturm EM, Maric J, Peinhaupt M, Luschnig P, Aringer I, Fauland A, Konya V et al.. (2016) Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung. J Allergy Clin Immunol, 137 (3): 833-43. [PMID:26792210]

19. Krause A, Zisowsky J, Strasser DS, Gehin M, Sidharta PN, Groenen PMA, Dingemanse J. (2016) Pharmacokinetic/Pharmacodynamic Modelling of Receptor Internalization with CRTH2 Antagonists to Optimize Dose Selection. Clin Pharmacokinet, 55 (7): 813-821. [PMID:26692193]

20. Liu J, Li AR, Wang Y, Johnson MG, Su Y, Shen W, Wang X, Lively S, Brown M, Lai S et al.. (2011) Discovery of AMG 853, a CRTH2 and DP Dual Antagonist. ACS Med Chem Lett, 2 (5): 326-30. [PMID:24900313]

21. Luker T, Bonnert R, Brough S, Cook AR, Dickinson MR, Dougall I, Logan C, Mohammed RT, Paine S, Sanganee HJ et al.. (2011) Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. Bioorg Med Chem Lett, 21 (21): 6288-92. [PMID:21944852]

22. Ly TW, Bacon KB. (2005) Small-molecule CRTH2 antagonists for the treatment of allergic inflammation: an overview. Expert Opin Investig Drugs, 14 (7): 769-73. [PMID:16022566]

23. Mathiesen JM, Christopoulos A, Ulven T, Royer JF, Campillo M, Heinemann A, Pardo L, Kostenis E. (2006) On the mechanism of interaction of potent surmountable and insurmountable antagonists with the prostaglandin D2 receptor CRTH2. Mol Pharmacol, 69 (4): 1441-53. [PMID:16418339]

24. Mjösberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B, Fokkens WJ, Cupedo T, Spits H. (2011) Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol, 12 (11): 1055-62. [PMID:21909091]

25. Monneret G, Cossette C, Gravel S, Rokach J, Powell WS. (2003) 15R-methyl-prostaglandin D2 is a potent and selective CRTH2/DP2 receptor agonist in human eosinophils. J Pharmacol Exp Ther, 304 (1): 349-55. [PMID:12490611]

26. Nagata K, Hirai H, Tanaka K, Ogawa K, Aso T, Sugamura K, Nakamura M, Takano S. (1999) CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s). FEBS Lett, 459 (2): 195-9. [PMID:10518017]

27. Nagata K, Tanaka K, Ogawa K, Kemmotsu K, Imai T, Yoshie O, Abe H, Tada K, Nakamura M, Sugamura K et al.. (1999) Selective expression of a novel surface molecule by human Th2 cells in vivo. J Immunol, 162 (3): 1278-86. [PMID:9973380]

28. Pettipher R, Vinall SL, Xue L, Speight G, Townsend ER, Gazi L, Whelan CJ, Armer RE, Payton MA, Hunter MG. (2012) Pharmacologic profile of OC000459, a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophils. J Pharmacol Exp Ther, 340 (2): 473-82. [PMID:22106101]

29. Royer JF, Schratl P, Lorenz S, Kostenis E, Ulven T, Schuligoi R, Peskar BA, Heinemann A. (2007) A novel antagonist of CRTH2 blocks eosinophil release from bone marrow, chemotaxis and respiratory burst. Allergy, 62 (12): 1401-9. [PMID:17714552]

30. Satoh T, Moroi R, Aritake K, Urade Y, Kanai Y, Sumi K, Yokozeki H, Hirai H, Nagata K, Hara T et al.. (2006) Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor. J Immunol, 177 (4): 2621-9. [PMID:16888024]

31. Sawyer N, Cauchon E, Chateauneuf A, Cruz RP, Nicholson DW, Metters KM, O'Neill GP, Gervais FG. (2002) Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2. Br J Pharmacol, 137 (8): 1163-72. [PMID:12466225]

32. Schmidt JA, Bell FM, Akam E, Marshall C, Dainty IA, Heinemann A, Dougall IG, Bonnert RV, Sargent CA. (2013) Biochemical and pharmacological characterization of AZD1981, an orally available selective DP2 antagonist in clinical development for asthma. Br J Pharmacol, 168 (7): 1626-38. [PMID:23146091]

33. Shichijo M, Sugimoto H, Nagao K, Inbe H, Encinas JA, Takeshita K, Bacon KB, Gantner F. (2003) Chemoattractant receptor-homologous molecule expressed on Th2 cells activation in vivo increases blood leukocyte counts and its blockade abrogates 13,14-dihydro-15-keto-prostaglandin D2-induced eosinophilia in rats. J Pharmacol Exp Ther, 307 (2): 518-25. [PMID:12975488]

34. Srinivas NR. (2015) First-in-man study of ACT-453859, a potent CRTH2 antagonist--Is the metabolite formation influenced by a polymorphic enzyme?. J Clin Pharmacol, 55 (12): 1432. [PMID:26761218]

35. Sugimoto H, Shichijo M, Iino T, Manabe Y, Watanabe A, Shimazaki M, Gantner F, Bacon KB. (2003) An orally bioavailable small molecule antagonist of CRTH2, ramatroban (BAY u3405), inhibits prostaglandin D2-induced eosinophil migration in vitro. J Pharmacol Exp Ther, 305 (1): 347-52. [PMID:12649388]

36. Sugimoto H, Shichijo M, Okano M, Bacon KB. (2005) CRTH2-specific binding characteristics of [3H]ramatroban and its effects on PGD2-, 15-deoxy-Delta12, 14-PGJ2- and indomethacin-induced agonist responses. Eur J Pharmacol, 524 (1-3): 30-7. [PMID:16256979]

37. Sykes D, Bradley M, Riddy D, Willard L, Powell-Herlaar E, Sandham D, Watson S, Bauer C, Dubois G, Charlton S. (2014) QAW039, a slowly dissociating CRTh2 antagonist with potential for improved clinical efficacy. Eur Respir J, 44 (Supl 58): 4074.

38. Sykes DA, Bradley ME, Riddy DM, Willard E, Reilly J, Miah A, Bauer C, Watson SJ, Sandham DA, Dubois G et al.. (2016) Fevipiprant (QAW039), a Slowly Dissociating CRTh2 Antagonist with the Potential for Improved Clinical Efficacy. Mol Pharmacol, 89 (5): 593-605. [PMID:26916831]

39. Ulven T, Kostenis E. (2005) Minor structural modifications convert the dual TP/CRTH2 antagonist ramatroban into a highly selective and potent CRTH2 antagonist. J Med Chem, 48 (4): 897-900. [PMID:15715457]

40. Wang L, Yao D, Deepak RNVK, Liu H, Xiao Q, Fan H, Gong W, Wei Z, Zhang C. (2018) Structures of the Human PGD2 Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition. Mol Cell, 72 (1): 48-59.e4. [PMID:30220562]

41. Wojno ED, Monticelli LA, Tran SV, Alenghat T, Osborne LC, Thome JJ, Willis C, Budelsky A, Farber DL, Artis D. (2015) The prostaglandin D₂ receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung. Mucosal Immunol, 8 (6): 1313-23. [PMID:25850654]

42. Xue L, Gyles SL, Wettey FR, Gazi L, Townsend E, Hunter MG, Pettipher R. (2005) Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol, 175 (10): 6531-6. [PMID:16272307]

43. Xue L, Salimi M, Panse I, Mjösberg JM, McKenzie AN, Spits H, Klenerman P, Ogg G. (2014) Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells. J Allergy Clin Immunol, 133 (4): 1184-94. [PMID:24388011]

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