Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDVVNS0)

• DOT Name: EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3)
• Synonyms: Developmentally-regulated endothelial cell locus 1 protein; Integrin-binding protein DEL1
• Gene Name: EDIL3
• Related Disease:
  Chromosomal disorder
  Adenocarcinoma
  Advanced cancer
  Allergic asthma
  Anxiety disorder
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cerebral infarction
  Chondrosarcoma
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Coronary atherosclerosis
  Endometrial cancer
  Endometrial carcinoma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Matthew-Wood syndrome
  Multiple sclerosis
  Myocardial ischemia
  Neoplasm
  Neuroblastoma
  Non-hodgkin lymphoma
  Non-small-cell lung cancer
  Osteoarthritis
  Pancreatic cancer
  Periodontal disease
  Plasma cell myeloma
  Psoriasis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Uterine fibroids
  Pulmonary disease
  Retinopathy
  Triple negative breast cancer
  Acute myelogenous leukaemia
  Ankylosing spondylitis
  Follicular lymphoma
  Intellectual disability
  Leiomyosarcoma
  Melanoma
  Periodontitis
  T-cell acute lymphoblastic leukaemia
• UniProt ID: EDIL3_HUMAN
• PDB ID: 4D90
• Pfam ID: PF00008 ; PF00754 ; PF12661
• Sequence:
  MKRSVAVWLLVGLSLGVPQFGKGDICDPNPCENGGICLPGLADGSFSCECPDGFTDPNCS
  SVVEVASDEEEPTSAGPCTPNPCHNGGTCEISEAYRGDTFIGYVCKCPRGFNGIHCQHNI
  NECEVEPCKNGGICTDLVANYSCECPGEFMGRNCQYKCSGPLGIEGGIISNQQITASSTH
  RALFGLQKWYPYYARLNKKGLINAWTAAENDRWPWIQINLQRKMRVTGVITQGAKRIGSP
  EYIKSYKIAYSNDGKTWAMYKVKGTNEDMVFRGNIDNNTPYANSFTPPIKAQYVRLYPQV
  CRRHCTLRMELLGCELSGCSEPLGMKSGHIQDYQITASSIFRTLNMDMFTWEPRKARLDK
  QGKVNAWTSGHNDQSQWLQVDLLVPTKVTGIITQGAKDFGHVQFVGSYKLAYSNDGEHWT
  VYQDEKQRKDKVFQGNFDNDTHRKNVIDPPIYARHIRILPWSWYGRITLRSELLGCTEEE
• Function: Promotes adhesion of endothelial cells through interaction with the alpha-v/beta-3 integrin receptor. Inhibits formation of vascular-like structures. May be involved in regulation of vascular morphogenesis of remodeling in embryonic development.

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chromosomal disorder	DISM5BB5	Definitive	Genetic Variation	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Allergic asthma	DISHF0H3	Strong	Biomarker	[4]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[5]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Cerebral infarction	DISR1WNP	Strong	Altered Expression	[8]
Chondrosarcoma	DIS4I7JB	Strong	Genetic Variation	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[10]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[8]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[11]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[14]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[14]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[15]
Multiple sclerosis	DISB2WZI	Strong	Altered Expression	[16]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[11]
Neuroblastoma	DISVZBI4	Strong	Genetic Variation	[17]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Genetic Variation	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[13]
Osteoarthritis	DIS05URM	Strong	Biomarker	[19]
Pancreatic cancer	DISJC981	Strong	Biomarker	[15]
Periodontal disease	DISJQHVN	Strong	Altered Expression	[20]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[21]
Psoriasis	DIS59VMN	Strong	Biomarker	[22]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[6]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[23]
Pulmonary disease	DIS6060I	moderate	Biomarker	[24]
Retinopathy	DISB4B0F	moderate	Biomarker	[25]
Triple negative breast cancer	DISAMG6N	moderate	Altered Expression	[26]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[27]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[28]
Follicular lymphoma	DISVEUR6	Limited	Genetic Variation	[29]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[30]
Leiomyosarcoma	DIS6COXM	Limited	Genetic Variation	[31]
Melanoma	DIS1RRCY	Limited	Altered Expression	[32]
Periodontitis	DISI9JOI	Limited	Biomarker	[24]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Genetic Variation	[29]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3) affects the response to substance of Fluorouracil.	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[36]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[37]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[39]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[40]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of EGF-like repeat and discoidin I-like domain-containing protein 3 (EDIL3).	[41]

References

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• [2] del(1)(q12) in adenocarcinomas of the prostate.Cancer Genet Cytogenet. 1996 Mar;87(1):79-81. doi: 10.1016/0165-4608(95)00213-8.
• [3] Del-1 overexpression potentiates lung cancer cell proliferation and invasion.Biochem Biophys Res Commun. 2015 Dec 4-11;468(1-2):92-8. doi: 10.1016/j.bbrc.2015.10.159. Epub 2015 Nov 9.
• [4] Developmental endothelial locus-1 (Del-1) antagonizes Interleukin-17-mediated allergic asthma.Immunol Cell Biol. 2018 May;96(5):526-535. doi: 10.1111/imcb.12023. Epub 2018 Mar 9.
• [5] Genetic Variants Associated With Anxiety and Stress-Related Disorders: A Genome-Wide Association Study and Mouse-Model Study.JAMA Psychiatry. 2019 Sep 1;76(9):924-932. doi: 10.1001/jamapsychiatry.2019.1119.
• [6] Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.J Urol. 2014 Aug;192(2):583-92. doi: 10.1016/j.juro.2014.02.035. Epub 2014 Feb 14.
• [7] Tumor derived EDIL3 modulates the expansion and osteoclastogenesis of myeloid derived suppressor cells in murine breast cancer model.J Bone Oncol. 2019 Apr 29;16:100238. doi: 10.1016/j.jbo.2019.100238. eCollection 2019 Jun.
• [8] Del-1 gene transfer induces cerebral angiogenesis in mice.Brain Res. 2008 Jul 11;1219:1-7. doi: 10.1016/j.brainres.2008.05.003. Epub 2008 May 10.
• [9] Deletion 1p in a low-grade chondrosarcoma in a patient with Ollier disease.Cancer Genet Cytogenet. 1998 Sep;105(2):128-33. doi: 10.1016/s0165-4608(98)00027-2.
• [10] Downregulation of developmentally regulated endothelial cell locus-1 inhibits the growth of colon cancer.J Biomed Sci. 2009;16(1):33. doi: 10.1186/1423-0127-16-33. Epub 2008 Dec 25.
• [11] Evaluation of Changes in the Expression Pattern of EDIL3 in Different Grades of Endometrial Cancer.Curr Pharm Biotechnol. 2019;20(6):483-488. doi: 10.2174/1389201020666190408112822.
• [12] EDIL3 is a novel regulator of epithelial-mesenchymal transition controlling early recurrence of hepatocellular carcinoma.J Hepatol. 2015 Oct;63(4):863-73. doi: 10.1016/j.jhep.2015.05.005. Epub 2015 May 14.
• [13] Prognostic Significance of EDIL3 Expression and Correlation with Mesenchymal Phenotype and Microvessel Density in Lung Adenocarcinoma.Sci Rep. 2017 Aug 17;7(1):8649. doi: 10.1038/s41598-017-08851-9.
• [14] Association of 12 polymorphic variants conferring genetic risk to lung cancer in Indian population: An extensive meta-analysis.Environ Mol Mutagen. 2017 Dec;58(9):688-700. doi: 10.1002/em.22149. Epub 2017 Oct 27.
• [15] Overexpressed EDIL3 predicts poor prognosis and promotes anchorage-independent tumor growth in human pancreatic cancer.Oncotarget. 2016 Jan 26;7(4):4226-40. doi: 10.18632/oncotarget.6772.
• [16] Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3-C/EBP pathway.Nat Commun. 2015 Sep 16;6:8272. doi: 10.1038/ncomms9272.
• [17] Cytogenetic analysis of primary neuroblastoma with del(1), del(14), hsr, and dmin chromosomes. Cancer Genet Cytogenet. 1991 Sep;55(2):231-4. doi: 10.1016/0165-4608(91)90082-6.
• [18] Detection of 14q32 translocations in B-cell malignancies by in situ hybridization with yeast artificial chromosome clones containing the human IgH gene locus.Blood. 1994 May 15;83(10):2962-9.
• [19] DEL1 protects against chondrocyte apoptosis through integrin binding.J Surg Res. 2018 Nov;231:1-9. doi: 10.1016/j.jss.2018.04.066. Epub 2018 May 30.
• [20] Clinical association between chronic periodontitis and the leukocyte extravasation inhibitors developmental endothelial locus-1 and pentraxin-3.Eur J Oral Sci. 2017 Aug;125(4):258-264. doi: 10.1111/eos.12357. Epub 2017 Jun 23.
• [21] Cytogenetic data as a prognostic factor in multiple myeloma patients: involvement of 1p12 region an adverse prognostic factor.Anticancer Res. 2004 Nov-Dec;24(6):4141-6.
• [22] mRNA and protein expression of the angiogenesis-related genes EDIL3, AMOT and ECM1 in mesenchymal stem cells in psoriatic dermis.Clin Exp Dermatol. 2016 Jul;41(5):533-40. doi: 10.1111/ced.12783. Epub 2015 Dec 8.
• [23] Uterine leiomyomata with deletions of Ip represent a distinct cytogenetic subgroup associated with unusual histologic features.Genes Chromosomes Cancer. 2006 Mar;45(3):304-12. doi: 10.1002/gcc.20291.
• [24] DEL-1-Regulated Immune Plasticity and Inflammatory Disorders.Trends Mol Med. 2019 May;25(5):444-459. doi: 10.1016/j.molmed.2019.02.010. Epub 2019 Mar 15.
• [25] Endogenous developmental endothelial locus-1 limits ischaemia-related angiogenesis by blocking inflammation.Thromb Haemost. 2017 Jun 2;117(6):1150-1163. doi: 10.1160/TH16-05-0354. Epub 2017 Apr 27.
• [26] MicroRNA-137 Inhibits Cancer Progression by Targeting Del-1 in Triple-Negative Breast Cancer Cells.Int J Mol Sci. 2019 Dec 6;20(24):6162. doi: 10.3390/ijms20246162.
• [27] Partial deletion of chromosome 1 in a case of acute myelocytic leukemia.Cancer Genet Cytogenet. 2002 Nov;139(1):60-2. doi: 10.1016/s0165-4608(02)00597-6.
• [28] Association study of polymorphisms rs4552569 and rs17095830 and the risk of ankylosing spondylitis in a Taiwanese population.PLoS One. 2013;8(1):e52801. doi: 10.1371/journal.pone.0052801. Epub 2013 Jan 4.
• [29] Development and validation of a quantitative polymerase chain reaction assay to evaluate minimal residual disease for T-cell acute lymphoblastic leukemia and follicular lymphoma.Am J Pathol. 1999 Apr;154(4):1023-35. doi: 10.1016/S0002-9440(10)65355-2.
• [30] Complex balanced translocation t(1;5;7)(p32.1;q14.3;p21.3) and two microdeletions del(1)(p31.1p31.1) and del(7)(p14.1p14.1) in a patient with features of Greig cephalopolysyndactyly and mental retardation.Am J Med Genet A. 2007 Nov 15;143A(22):2738-43. doi: 10.1002/ajmg.a.32017.
• [31] Cytogenetic observations in a human gastric leiomyosarcoma.Cancer Genet Cytogenet. 1989 Feb;37(2):215-20. doi: 10.1016/0165-4608(89)90051-4.
• [32] Inhibition of p38/MK2 Signaling Prevents Vascular Invasion of Melanoma.J Invest Dermatol. 2020 Apr;140(4):878-890.e5. doi: 10.1016/j.jid.2019.08.451. Epub 2019 Oct 14.
• [33] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [34] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [35] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [36] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [37] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [38] Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2. Am J Respir Cell Mol Biol. 2008 Sep;39(3):312-23. doi: 10.1165/rcmb.2008-0012OC. Epub 2008 Apr 17.
• [39] Gene expression changes associated with altered growth and differentiation in benzo[a]pyrene or arsenic exposed normal human epidermal keratinocytes. J Appl Toxicol. 2008 May;28(4):491-508.
• [40] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [41] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
• [42] 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.