Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3E070F)

• DOT Name: Intercellular adhesion molecule 2 (ICAM2)
• Synonyms: ICAM-2; CD antigen CD102
• Gene Name: ICAM2
• Related Disease:
  Abdominal aortic aneurysm
  Advanced cancer
  Barrett esophagus
  Carcinoma of esophagus
  Esophageal cancer
  Gastric cancer
  HIV infectious disease
  Lung cancer
  Lung carcinoma
  Malignant mesothelioma
  Neoplasm of esophagus
  Pancreatic cancer
  Stomach cancer
  Systemic sclerosis
  Ulcerative colitis
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Neoplasm
  Neuroblastoma
• UniProt ID: ICAM2_HUMAN
• PDB ID: 1ZXQ
• Pfam ID: PF03921
• Sequence:
  MSSFGYRTLTVALFTLICCPGSDEKVFEVHVRPKKLAVEPKGSLEVNCSTTCNQPEVGGL
  ETSLDKILLDEQAQWKHYLVSNISHDTVLQCHFTCSGKQESMNSNVSVYQPPRQVILTLQ
  PTLVAVGKSFTIECRVPTVEPLDSLTLFLFRGNETLHYETFGKAAPAPQEATATFNSTAD
  REDGHRNFSCLAVLDLMSRGGNIFHKHSAPKMLEIYEPVSDSQMVIIVTVVSVLLSLFVT
  SVLLCFIFGQHLRQQRMGTYGVRAAWRRLPQAFRP
• Function: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). ICAM2 may play a role in lymphocyte recirculation by blocking LFA-1-dependent cell adhesion. It mediates adhesive interactions important for antigen-specific immune response, NK-cell mediated clearance, lymphocyte recirculation, and other cellular interactions important for immune response and surveillance.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  .tural killer cell mediated cytotoxicity (hsa04650)
• Reactome Pathway:
  Integrin cell surface interactions (R-HSA-216083)
  CD209 (DC-SIGN) signaling (R-HSA-5621575)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Abdominal aortic aneurysm	DISD06OF	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[3]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[3]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[3]
Gastric cancer	DISXGOUK	Strong	Biomarker	[4]
HIV infectious disease	DISO97HC	Strong	Biomarker	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[7]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[3]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[8]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[10]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[11]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[4]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[4]
Neoplasm	DISZKGEW	Limited	Biomarker	[12]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Intercellular adhesion molecule 2 (ICAM2).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Intercellular adhesion molecule 2 (ICAM2).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Intercellular adhesion molecule 2 (ICAM2).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Intercellular adhesion molecule 2 (ICAM2).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Intercellular adhesion molecule 2 (ICAM2).	[17]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Intercellular adhesion molecule 2 (ICAM2).	[19]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Intercellular adhesion molecule 2 (ICAM2).	[4]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Intercellular adhesion molecule 2 (ICAM2).	[21]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Intercellular adhesion molecule 2 (ICAM2).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Intercellular adhesion molecule 2 (ICAM2).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Intercellular adhesion molecule 2 (ICAM2).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Intercellular adhesion molecule 2 (ICAM2).	[26]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Intercellular adhesion molecule 2 (ICAM2).	[27]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Intercellular adhesion molecule 2 (ICAM2).	[25]
PFI-1	DMVFK3J	Investigative	PFI-1 decreases the expression of Intercellular adhesion molecule 2 (ICAM2).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Intercellular adhesion molecule 2 (ICAM2).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Intercellular adhesion molecule 2 (ICAM2).	[24]

References

• [1] Complement regulator CD59 protects against angiotensin II-induced abdominal aortic aneurysms in mice.Circulation. 2010 Mar 23;121(11):1338-46. doi: 10.1161/CIRCULATIONAHA.108.844589. Epub 2010 Mar 8.
• [2] Identification and characterization of the intercellular adhesion molecule-2 gene as a novel p53 target.Oncotarget. 2016 Sep 20;7(38):61426-61437. doi: 10.18632/oncotarget.11366.
• [3] Investigation of intercellular adhesion molecules (ICAMs) gene expressions in patients with Barrett's esophagus.Tumour Biol. 2014 May;35(5):4907-12. doi: 10.1007/s13277-014-1644-3. Epub 2014 Jan 29.
• [4] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [5] The role of trophoblast cell receptor expression in HIV-1 passage across the placenta in pre-eclampsia: an observational study.BJOG. 2017 May;124(6):920-928. doi: 10.1111/1471-0528.14311. Epub 2016 Oct 3.
• [6] Integrative Analysis of CD133 mRNA in Human Cancers Based on Data Mining.Stem Cell Rev Rep. 2019 Feb;15(1):23-34. doi: 10.1007/s12015-018-9865-2.
• [7] Early detection of malignant pleural mesothelioma in asbestos-exposed individuals with a noninvasive proteomics-based surveillance tool.PLoS One. 2012;7(10):e46091. doi: 10.1371/journal.pone.0046091. Epub 2012 Oct 3.
• [8] Expression of intercellular adhesion molecule (ICAM)-1 or ICAM-2 is critical in determining sensitivity of pancreatic cancer cells to cytolysis by human gammadelta-T cells: implications in the design of gammadelta-T-cell-based immunotherapies for pancreatic cancer.J Gastroenterol Hepatol. 2009 May;24(5):900-11. doi: 10.1111/j.1440-1746.2008.05668.x. Epub 2008 Nov 3.
• [9] ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.Clin Cancer Res. 2004 Jul 15;10(14):4885-92. doi: 10.1158/1078-0432.CCR-0393-03.
• [10] Endothelial Cells Expressing Endothelial and Mesenchymal Cell Gene Products in Lung Tissue From Patients With Systemic Sclerosis-Associated Interstitial Lung Disease.Arthritis Rheumatol. 2016 Jan;68(1):210-7. doi: 10.1002/art.39421.
• [11] Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986-2005: a KASID study.Inflamm Bowel Dis. 2008 Apr;14(4):542-9. doi: 10.1002/ibd.20310.
• [12] ICAM-2 confers a non-metastatic phenotype in neuroblastoma cells by interaction with -actinin.Oncogene. 2015 Mar 19;34(12):1553-62. doi: 10.1038/onc.2014.87. Epub 2014 Apr 7.
• [13] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [14] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [15] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [18] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [19] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [20] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [21] 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.
• [22] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [23] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [24] 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.
• [25] BRD4 is a novel therapeutic target for liver fibrosis. Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15713-8. doi: 10.1073/pnas.1522163112. Epub 2015 Dec 7.
• [26] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [27] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.