Target Information

Target General Infomation
Target ID
T68782
Former ID
TTDR00802
Target Name
Prostaglandin D2 receptor
Gene Name
PTGDR
Synonyms
PGD receptor; Prostanoid DP receptor; PTGDR
Target Type
Clinical Trial
Disease Allergy [ICD9: 995.3; ICD10: T78.4]
Asthma [ICD10: J45]
Allergic rhinitis [ICD9: 472.0, 477, 995.3; ICD10: J00, J30, J31.0, T78.4]
Atopic dermatitis [ICD9: 691.8, 692.9; ICD10: L00-L99]
Dyslipidaemias [ICD9: 272; ICD10: E78]
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89]
Rhinitis [ICD9: 472.0, 477; ICD10: J00, J30, J31.0]
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Thrombosis [ICD9: 437.6, 453, 671.5, 671.9; ICD10: I80-I82]
Thromboembolism [ICD9: 437.6, 453, 671.5, 671.9; ICD10: I80-I82]
Function
Receptor for prostaglandin D2 (PGD2). 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 (By similarity).
BioChemical Class
GPCR rhodopsin
Target Validation
T68782
UniProt ID
Q13258
Sequence
MKSPFYRCQNTTSVEKGNSAVMGGVLFSTGLLGNLLALGLLARSGLGWCSRRPLRPLPSV
FYMLVCGLTVTDLLGKCLLSPVVLAAYAQNRSLRVLAPALDNSLCQAFAFFMSFFGLSST
LQLLAMALECWLSLGHPFFYRRHITLRLGALVAPVVSAFSLAFCALPFMGFGKFVQYCPG
TWCFIQMVHEEGSLSVLGYSVLYSSLMALLVLATVLCNLGAMRNLYAMHRRLQRHPRSCT
RDCAEPRADGREASPQPLEELDHLLLLALMTVLFTMCSLPVIYRAYYGAFKDVKEKNRTS
EEAEDLRALRFLSVISIVDPWIFIIFRSPVFRIFFHKIFIRPLRYRSRCSNSTNMESSL
Drugs and Mode of Action
Drug(s) LAROPIPRANT Drug Info Phase 4 Discovery agent [1], [2]
QAW-039 Drug Info Phase 3 Asthma [3]
AMG 853 Drug Info Phase 2 Asthma [4]
MK-1029 Drug Info Phase 2 Asthma [5]
ONO-4053 Drug Info Phase 2 Allergic rhinitis [6]
S-555739 Drug Info Phase 2 Allergy [7]
TS-022 Drug Info Phase 2 Atopic dermatitis [8]
192C86 Drug Info Phase 1 Thrombosis [9]
SAR-389644 Drug Info Phase 1 Allergic rhinitis [10]
PGF2alpha Drug Info Clinical trial Solid tumours [11]
Laropiprant+niacin Drug Info Discontinued in Phase 3 Dyslipidaemias [12]
S-5751 Drug Info Discontinued in Phase 2 Rhinitis [13], [14]
ONO-4127Na Drug Info Discontinued in Phase 1 Allergic rhinitis [15]
ZK-118182 Drug Info Terminated Thromboembolism [16], [17]
Agonist 15-deoxy-Delta12,14-PGJ2 Drug Info [18]
butaprost (free acid form) Drug Info [19]
BW 245C Drug Info [20]
carbacyclin Drug Info [19]
cloprostenol Drug Info [19]
Delta12-PGJ2 Drug Info [18]
L-644,698 Drug Info [21]
L-888,291 Drug Info [22]
PGD2 Drug Info [21]
PGF2alpha Drug Info [19]
PGJ2 Drug Info [18]
RS 93520 Drug Info [23]
SQ-27986 Drug Info [23]
TS-022 Drug Info [24]
U46619 Drug Info [19]
ZK110841 Drug Info [18]
[3H]PGD2 Drug Info [25]
Modulator 192C86 Drug Info [26]
AMG 853 Drug Info
TTH 03-001 Drug Info [27]
ZK-118182 Drug Info [28]
Antagonist AH6809 Drug Info [19]
BWA868C Drug Info [18]
Laropiprant+niacin Drug Info [29]
ONO-4053 Drug Info [30]
ONO-4127Na Drug Info [31]
ONO-AE3-237 Drug Info [32]
Prostaglandin D2 antagonists Drug Info [27]
QAW-039 Drug Info [33]
S-555739 Drug Info [7]
S-5751 Drug Info [34]
SAR-389644 Drug Info [35]
[3H]BWA868C Drug Info [36]
Inhibitor DIASTEREOMER 2 Drug Info [37]
LAROPIPRANT Drug Info [37]
MK-1029 Drug Info [38]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Neuroactive ligand-receptor interaction
Pathway Interaction Database Thromboxane A2 receptor signaling
PathWhiz Pathway Intracellular Signalling Through PGD2 receptor and Prostaglandin D2
Reactome Prostanoid ligand receptors
G alpha (s) signalling events
WikiPathways Prostaglandin Synthesis and Regulation
GPCRs, Class A Rhodopsin-like
Small Ligand GPCRs
GPCR ligand binding
GPCR downstream signaling
References
REF 1ClinicalTrials.gov (NCT01126073) Niacin/Laropiprant and Endothelial Function. U.S. National Institutes of Health.
REF 2(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 3ClinicalTrials.gov (NCT02563067) Study of Efficacy and Safety of QAW039 in Patients With Severe Asthma Inadequately Controlled With Standard of Care Asthma Treatment.
REF 4ClinicalTrials.gov (NCT01018550) AMG 853 Phase 2 Study in Subjects With Inadequately Controlled Asthma. U.S. National Institutes of Health.
REF 5ClinicalTrials.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 6ClinicalTrials.gov (NCT01748344) Phase II Study Evaluating ONO-4053 and Cetirizine in Subjects With Seasonal Allergic Rhinitis. U.S. National Institutes of Health.
REF 7Clinical pipeline report, company report or official report of Shionogi (2011).
REF 8ClinicalTrials.gov (NCT00914186) Study of TS-022 in Adult Patients With Atopic Dermatitis With Pruritus (POC). U.S. National Institutes of Health.
REF 9The 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 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025865)
REF 11Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature. 2012 Sep 13;489(7415):278-81.
REF 12ClinicalTrials.gov (NCT01054508) Effect of Tredaptive on Serum Lipoproteins and Inflammatory Markers. U.S. National Institutes of Health.
REF 13(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 14Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012090)
REF 15Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018932)
REF 16(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: 1890).
REF 17Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003331)
REF 18Characterization 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 19The 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 20Ligand 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 21A 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 22Identification of a potent and selective synthetic agonist at the CRTH2 receptor. Mol Pharmacol. 2005 Jun;67(6):1834-9. Epub 2005 Mar 8.
REF 23Affinities, 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 24Effects of TS-022, a newly developed prostanoid DP1 receptor agonist, on experimental pruritus, cutaneous barrier disruptions and atopic dermatitis in mice. Eur J Pharmacol. 2007 Feb 5;556(1-3):207-14. Epub 2006 Nov 3.
REF 25GW627368X ((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 26Prostanoid receptor antagonists: development strategies and therapeutic applications. Br J Pharmacol. 2009 September; 158(1): 104-145.
REF 27(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: 338).
REF 28Characterization 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 29Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
REF 30Effect 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 31Sleep-wake regulation by prostaglandin D2 and adenosine. Brain Nerve. 2012 Jun;64(6):621-8.
REF 32Prostaglandin 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 33Effect 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 34Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
REF 35US patent application no. 2008,0300,217, Combination therapy with fumaric acid esters for the treatment of autoimmune and,or inflammatory disorders.
REF 36Pharmacology 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 37J 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 38Update 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.

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