Details of Drug Off-Target (DOT)

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

• DOT Name: Adenosine receptor A2b (ADORA2B)
• Gene Name: ADORA2B
• UniProt ID: AA2BR_HUMAN
• PDB ID: 7XY6; 7XY7; 8HDO; 8HDP
• Pfam ID: PF00001
• Sequence:
  MLLETQDALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFA
  IPFAITISLGFCTDFYGCLFLACFVLVLTQSSIFSLLAVAVDRYLAICVPLRYKSLVTGT
  RARGVIAVLWVLAFGIGLTPFLGWNSKDSATNNCTEPWDGTTNESCCLVKCLFENVVPMS
  YMVYFNFFGCVLPPLLIMLVIYIKIFLVACRQLQRTELMDHSRTTLQREIHAAKSLAMIV
  GIFALCWLPVHAVNCVTLFQPAQGKNKPKWAMNMAILLSHANSVVNPIVYAYRNRDFRYT
  FHKIISRYLLCQADVKSGNGQAGVQPALGVGL
• Function: Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  Neuroactive ligand-receptor interaction (hsa04080)
  Vascular smooth muscle contraction (hsa04270)
  Alcoholism (hsa05034)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Surfactant metabolism (R-HSA-5683826)
  ADORA2B mediated anti-inflammatory cytokines production (R-HSA-9660821)
  Adenosine P1 receptors (R-HSA-417973)

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
Cisplatin	DMRHGI9	Approved	Adenosine receptor A2b (ADORA2B) affects the response to substance of Cisplatin.	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Adenosine receptor A2b (ADORA2B).	[1]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Adenosine receptor A2b (ADORA2B).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Adenosine receptor A2b (ADORA2B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Adenosine receptor A2b (ADORA2B).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Adenosine receptor A2b (ADORA2B).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adenosine receptor A2b (ADORA2B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Adenosine receptor A2b (ADORA2B).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Adenosine receptor A2b (ADORA2B).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Adenosine receptor A2b (ADORA2B).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Adenosine receptor A2b (ADORA2B).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Adenosine receptor A2b (ADORA2B).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Adenosine receptor A2b (ADORA2B).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Adenosine receptor A2b (ADORA2B).	[11]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Adenosine receptor A2b (ADORA2B).	[12]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Adenosine receptor A2b (ADORA2B).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Adenosine receptor A2b (ADORA2B).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adenosine receptor A2b (ADORA2B).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Adenosine receptor A2b (ADORA2B).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Adenosine receptor A2b (ADORA2B).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Adenosine receptor A2b (ADORA2B).	[20]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
ZM-241385	DMWQ38G	Terminated	ZM-241385 affects the binding of Adenosine receptor A2b (ADORA2B).	[17]
GNF-PF-2224	DM26UKN	Investigative	GNF-PF-2224 affects the binding of Adenosine receptor A2b (ADORA2B).	[21]

References

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• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Adenosine receptor expression in rheumatoid synovium: a basis for methotrexate action. Arthritis Res Ther. 2012 Jun 8;14(3):R138. doi: 10.1186/ar3871.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [13] MIP-1beta, a novel biomarker for in vitro sensitization test using human monocytic cell line. Toxicol In Vitro. 2006 Aug;20(5):736-42.
• [14] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [15] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [16] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [17] Synthesis and biological evaluation of a new series of 1,2,4-triazolo[1,5-a]-1,3,5-triazines as human A(2A) adenosine receptor antagonists with improved water solubility. J Med Chem. 2011 Feb 10;54(3):877-89. doi: 10.1021/jm101349u. Epub 2011 Jan 7.
• [18] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [19] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [20] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [21] Pyrimidine derivatives as potent and selective A3 adenosine receptor antagonists. J Med Chem. 2011 Jan 27;54(2):457-71. doi: 10.1021/jm100843z. Epub 2010 Dec 27.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.