Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCSMVF1)

• DOT Name: Prostaglandin D2 receptor 2 (PTGDR2)
• Synonyms: Chemoattractant receptor-homologous molecule expressed on Th2 cells; G-protein coupled receptor 44; CD antigen CD294
• Gene Name: PTGDR2
• UniProt ID: PD2R2_HUMAN
• PDB ID: 6D26; 6D27; 7M8W
• Pfam ID: PF00001
• Sequence:
  MSANATLKPLCPILEQMSRLQSHSNTSIRYIDHAAVLLHGLASLLGLVENGVILFVVGCR
  MRQTVVTTWVLHLALSDLLASASLPFFTYFLAVGHSWELGTTFCKLHSSIFFLNMFASGF
  LLSAISLDRCLQVVRPVWAQNHRTVAAAHKVCLVLWALAVLNTVPYFVFRDTISRLDGRI
  MCYYNVLLLNPGPDRDATCNSRQVALAVSKFLLAFLVPLAIIASSHAAVSLRLQHRGRRR
  PGRFVRLVAAVVAAFALCWGPYHVFSLLEARAHANPGLRPLVWRGLPFVTSLAFFNSVAN
  PVLYVLTCPDMLRKLRRSLRTVLESVLVDDSELGGAGSSRRRRTSSTARSASPLALCSRP
  EEPRGPARLLGWLLGSCAASPQTGPLNRALSSTSS
• Function: Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses.
• Tissue Specificity: Widespread expression. High expression in stomach, small intestine, heart and thymus. Intermediate expression in colon, spinal cord and peripheral blood and low expression in brain, skeletal muscle and spleen. Expressed also on Th2- and Tc2- type cells, eosinophils and basophils.
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Prostanoid ligand receptors (R-HSA-391908)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Prostaglandin D2 receptor 2 (PTGDR2) affects the response to substance of Aspirin.	[9]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Prostaglandin D2 receptor 2 (PTGDR2).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Prostaglandin D2 receptor 2 (PTGDR2).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Prostaglandin D2 receptor 2 (PTGDR2).	[3]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the activity of Prostaglandin D2 receptor 2 (PTGDR2).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Prostaglandin D2 receptor 2 (PTGDR2).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Prostaglandin D2 receptor 2 (PTGDR2).	[7]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Prostaglandin D2 receptor 2 (PTGDR2).	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Prostaglandin D2 receptor 2 (PTGDR2).	[6]

References

• [1] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [2] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [3] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [4] Cutting edge: agonistic effect of indomethacin on a prostaglandin D2 receptor, CRTH2. J Immunol. 2002 Feb 1;168(3):981-5. doi: 10.4049/jimmunol.168.3.981.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [9] Genetic and ethnic risk factors associated with drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2010 Aug;10(4):280-90. doi: 10.1097/ACI.0b013e32833b1eb3.