Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRRZT7W)

• DOT Name: Anterior gradient protein 2 homolog (AGR2)
• Synonyms: AG-2; hAG-2; HPC8; Secreted cement gland protein XAG-2 homolog
• Gene Name: AGR2
• Related Disease: Respiratory infections, recurrent, and failure to thrive with or without diarrhea
• UniProt ID: AGR2_HUMAN
• PDB ID: 2LNS; 2LNT
• Pfam ID: PF13899
• Sequence:
  MEKIPVSAFLLLVALSYTLARDTTVKPGAKKDTKDSRPKLPQTLSRGWGDQLIWTQTYEE
  ALYKSKTSNKPLMIIHHLDECPHSQALKKVFAENKEIQKLAEQFVLLNLVYETTDKHLSP
  DGQYVPRIMFVDPSLTVRADITGRYSNRLYAYEPADTALLLDNMKKALKLLKTEL
• Function: Required for MUC2 post-transcriptional synthesis and secretion. May play a role in the production of mucus by intestinal cells. Proto-oncogene that may play a role in cell migration, cell differentiation and cell growth. Promotes cell adhesion.
• Tissue Specificity: Expressed strongly in trachea, lung, stomach, colon, prostate and small intestine. Expressed weakly in pituitary gland, salivary gland, mammary gland, bladder, appendix, ovary, fetal lung, uterus, pancreas, kidney, fetal kidney, testis, placenta, thyroid gland and in estrogen receptor (ER)-positive breast cancer cell lines.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Respiratory infections, recurrent, and failure to thrive with or without diarrhea	DISHOGFT	Strong	Autosomal recessive	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Anterior gradient protein 2 homolog (AGR2) affects the response to substance of Fulvestrant.	[21]
Capecitabine	DMTS85L	Approved	Anterior gradient protein 2 homolog (AGR2) increases the response to substance of Capecitabine.	[22]

23 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 Anterior gradient protein 2 homolog (AGR2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Anterior gradient protein 2 homolog (AGR2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Anterior gradient protein 2 homolog (AGR2).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Anterior gradient protein 2 homolog (AGR2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Anterior gradient protein 2 homolog (AGR2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Anterior gradient protein 2 homolog (AGR2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Anterior gradient protein 2 homolog (AGR2).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Anterior gradient protein 2 homolog (AGR2).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Anterior gradient protein 2 homolog (AGR2).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Anterior gradient protein 2 homolog (AGR2).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Anterior gradient protein 2 homolog (AGR2).	[8]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Anterior gradient protein 2 homolog (AGR2).	[11]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Anterior gradient protein 2 homolog (AGR2).	[12]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Anterior gradient protein 2 homolog (AGR2).	[13]
Prasterone	DM67VKL	Approved	Prasterone affects the expression of Anterior gradient protein 2 homolog (AGR2).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Anterior gradient protein 2 homolog (AGR2).	[15]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Anterior gradient protein 2 homolog (AGR2).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Anterior gradient protein 2 homolog (AGR2).	[17]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin increases the expression of Anterior gradient protein 2 homolog (AGR2).	[18]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 increases the expression of Anterior gradient protein 2 homolog (AGR2).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Anterior gradient protein 2 homolog (AGR2).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Anterior gradient protein 2 homolog (AGR2).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Anterior gradient protein 2 homolog (AGR2).	[20]

References

• [1] Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease. Genes Immun. 2006 Jan;7(1):11-8. doi: 10.1038/sj.gene.6364263.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells. Br J Nutr. 2008 Apr;99(4):703-8.
• [12] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [13] Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
• [14] Comparative effects of DHEA and DHT on gene expression in human LNCaP prostate cancer cells. Anticancer Res. 2006 Sep-Oct;26(5A):3205-15.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [16] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [17] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [18] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [19] Gene expression profiling in Caco-2 human colon cells exposed to TCDD, benzo[a]pyrene, and natural Ah receptor agonists from cruciferous vegetables and citrus fruits. Toxicol In Vitro. 2008 Mar;22(2):396-410.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [21] Anterior gradient-2 plays a critical role in breast cancer cell growth and survival by modulating cyclin D1, estrogen receptor-alpha and survivin. Breast Cancer Res. 2010;12(3):R32. doi: 10.1186/bcr2586. Epub 2010 Jun 4.
• [22] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.