Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNVEIR)

• DTT Name: Prostaglandin D2 receptor (PTGDR)
• Synonyms: Prostanoid DP receptor; PGD2 receptor; PGD receptor
• Gene Name: PTGDR
• DTT Type: Clinical trial target; [1]
• BioChemical Class: GPCR rhodopsin
• UniProt ID: PD2R_HUMAN
• TTD ID: T68782
• Sequence:
  MKSPFYRCQNTTSVEKGNSAVMGGVLFSTGLLGNLLALGLLARSGLGWCSRRPLRPLPSV
  FYMLVCGLTVTDLLGKCLLSPVVLAAYAQNRSLRVLAPALDNSLCQAFAFFMSFFGLSST
  LQLLAMALECWLSLGHPFFYRRHITLRLGALVAPVVSAFSLAFCALPFMGFGKFVQYCPG
  TWCFIQMVHEEGSLSVLGYSVLYSSLMALLVLATVLCNLGAMRNLYAMHRRLQRHPRSCT
  RDCAEPRADGREASPQPLEELDHLLLLALMTVLFTMCSLPVIYRAYYGAFKDVKEKNRTS
  EEAEDLRALRFLSVISIVDPWIFIIFRSPVFRIFFHKIFIRPLRYRSRCSNSTNMESSL
• 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).
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Prostanoid ligand receptors (R-HSA-391908)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LAROPIPRANT	DM5FABJ	Coronary heart disease	BA80.Z	Phase 4	[1]

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
QAW-039	DMPCFXN	Asthma	CA23	Phase 3	[2]
Setipiprant	DMZ61IA	Asthma	CA23	Phase 3	[3]
AMG 853	DM973N4	Asthma	CA23	Phase 2	[4]
MK-1029	DM8ZTW7	Asthma	CA23	Phase 2	[5]
ONO-4053	DMX4MVP	Allergic rhinitis	CA08.0	Phase 2	[6]
S-555739	DMXDVNZ	Allergy	4A80-4A85	Phase 2	[7]
TS-022	DMMNXIW	Atopic dermatitis	EA80	Phase 2	[8]
192C86	DMQ8NTZ	Thrombosis	DB61-GB90	Phase 1	[9]
MK-1092	DMHS79I	Type-1 diabetes	5A10	Phase 1	[10]
SAR-389644	DMA6O9R	Allergic rhinitis	CA08.0	Phase 1	[11]
PGF2alpha	DM4XAU7	Solid tumour/cancer	2A00-2F9Z	Clinical trial	[12]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
S-5751	DM2X6ME	Rhinitis	FA20	Discontinued in Phase 2	[13]
ONO-4127	DMUSKY0	Allergic rhinitis	CA08.0	Discontinued in Phase 1	[14]
ZK-118182	DMJZH7N	Thrombosis	DB61-GB90	Terminated	[15]

19 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
15-deoxy-Delta12,14-PGJ2	DMNDECA	Discovery agent	N.A.	Investigative	[16]
AH6809	DMKN3R9	Discovery agent	N.A.	Investigative	[12]
butaprost (free acid form)	DM5MZHP	Discovery agent	N.A.	Investigative	[12]
BW 245C	DMA0FO5	Discovery agent	N.A.	Investigative	[17]
BWA868C	DMU9LQW	Discovery agent	N.A.	Investigative	[18]
carbacyclin	DMMBQYE	Discovery agent	N.A.	Investigative	[12]
cloprostenol	DMH01JV	Discovery agent	N.A.	Investigative	[12]
Delta12-PGJ2	DMB6ADI	Discovery agent	N.A.	Investigative	[16]
DIASTEREOMER 2	DM3CQV6	Discovery agent	N.A.	Investigative	[1]
L-644,698	DMENUOD	Discovery agent	N.A.	Investigative	[19]
L-888,291	DMMAIQ2	Discovery agent	N.A.	Investigative	[20]
ONO-AE3-237	DMGA4W5	Discovery agent	N.A.	Investigative	[21]
PGD2	DMYDW6J	Discovery agent	N.A.	Investigative	[19]
PGJ2	DMR2LTC	Discovery agent	N.A.	Investigative	[16]
RS 93520	DM8SGTQ	Discovery agent	N.A.	Investigative	[22]
SQ-27986	DMLPN95	Discovery agent	N.A.	Investigative	[22]
TTH 03-001	DM6NZFH	Pain	MG30-MG3Z	Investigative	[23]
U46619	DM13FX4	Discovery agent	N.A.	Investigative	[12]
ZK110841	DMY3SUZ	Discovery agent	N.A.	Investigative	[16]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Atopic dermatitis	EA90	Skin	7.32E-02	-0.05	-0.2
Asthma	CA23	Nasal and bronchial airway	7.32E-02	-0.14	-0.23

References

• [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.
• [2] 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.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients.J Allergy Clin Immunol.2013 Feb;131(2):339-45.
• [5] 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.
• [6] 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.
• [7] Clinical pipeline report, company report or official report of Shionogi (2011).
• [8] 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.
• [9] Prostanoid receptor antagonists: development strategies and therapeutic applications. Br J Pharmacol. 2009 September; 158(1): 104-145.
• [10] The challenge of modulating -cell autoimmunity in type 1 diabetes. Lancet Diabetes Endocrinol. 2019 Jan;7(1):52-64.
• [11] US patent application no. 2008,0300,217, Combination therapy with fumaric acid esters for the treatment of autoimmune and,or inflammatory disorders.
• [12] 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.
• [13] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
• [14] Sleep-wake regulation by prostaglandin D2 and adenosine. Brain Nerve. 2012 Jun;64(6):621-8.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Identification of a potent and selective synthetic agonist at the CRTH2 receptor. Mol Pharmacol. 2005 Jun;67(6):1834-9.
• [21] 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.
• [22] 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.
• [23] 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: 338).