Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWIWGL6)

DOT Name	Artemin (ARTN)
Synonyms	Enovin; Neublastin
Gene Name	ARTN
Related Disease	Tuberculosis ( ) Adenocarcinoma ( ) Advanced cancer ( ) Alzheimer disease ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Breast cancer ( ) Breast neoplasm ( ) Colorectal carcinoma ( ) Congestive heart failure ( ) Endometrial carcinoma ( ) Endometriosis ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) High blood pressure ( ) Hirschsprung disease ( ) Immunodeficiency ( ) Liver cirrhosis ( ) Lung cancer ( ) Lung carcinoma ( ) Major depressive disorder ( ) Male infertility ( ) Melanoma ( ) Mental disorder ( ) Metastatic malignant neoplasm ( ) Myocardial infarction ( ) Neoplasm ( ) Nephropathy ( ) Neuroblastoma ( ) Non-small-cell lung cancer ( ) Obesity ( ) Oligospermia ( ) Peripheral neuropathy ( ) Pneumocystis pneumonia ( ) Sexually transmitted infection ( ) Type-1/2 diabetes ( ) Autoimmune disease ( ) Cardiovascular disease ( ) Head and neck cancer ( ) Head and neck carcinoma ( ) HIV infectious disease ( ) Stroke ( ) Acute myelogenous leukaemia ( ) Breast carcinoma ( ) Chronic kidney disease ( ) Immune system disorder ( ) Malaria ( ) Neuralgia ( ) Pancreatic cancer ( )
UniProt ID	ARTN_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2ASK; 2GH0; 2GYR; 2GYZ; 6Q2S
Pfam ID	PF00019
Sequence	MELGLGGLSTLSHCPWPRQQPALWPTLAALALLSSVAEASLGSAPRSPAPREGPPPVLAS PAGHLPGGRTARWCSGRARRPPPQPSRPAPPPPAPPSALPRGGRAARAGGPGSRARAAGA RGCRLRSQLVPVRALGLGHRSDELVRFRFCSGSCRRARSPHDLSLASLLGAGALRPPPGS RPVSQPCCRPTRYEAVSFMDVNSTWRTVDRLSATACGCLG
Function	Ligand for the GFR-alpha-3-RET receptor complex but can also activate the GFR-alpha-1-RET receptor complex. Supports the survival of sensory and sympathetic peripheral neurons in culture and also supports the survival of dopaminergic neurons of the ventral mid-brain. Strong attractant of gut hematopoietic cells thus promoting the formation Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue.
Tissue Specificity	Ubiquitous. Expressed at high levels in peripheral tissues including prostate, placenta, pancreas, heart, kidney, pituitary gland, lung and testis. Expressed at low levels in the brain.
KEGG Pathway	MAPK sig.ling pathway (hsa04010 ) PI3K-Akt sig.ling pathway (hsa04151 )
Reactome Pathway	RAF/MAP kinase cascade (R-HSA-5673001 ) RET signaling (R-HSA-8853659 ) NCAM1 interactions (R-HSA-419037 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[8]
Endometriosis	DISX1AG8	Strong	Biomarker	[9]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
High blood pressure	DISY2OHH	Strong	Biomarker	[12]
Hirschsprung disease	DISUUSM1	Strong	Biomarker	[13]
Immunodeficiency	DIS093I0	Strong	Biomarker	[14]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[2]
Lung carcinoma	DISTR26C	Strong	Biomarker	[2]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[16]
Male infertility	DISY3YZZ	Strong	Biomarker	[17]
Melanoma	DIS1RRCY	Strong	Biomarker	[18]
Mental disorder	DIS3J5R8	Strong	Biomarker	[19]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[20]
Myocardial infarction	DIS655KI	Strong	Biomarker	[21]
Neoplasm	DISZKGEW	Strong	Biomarker	[22]
Nephropathy	DISXWP4P	Strong	Biomarker	[23]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Genetic Variation	[24]
Oligospermia	DIS6YJF3	Strong	Biomarker	[25]
Peripheral neuropathy	DIS7KN5G	Strong	Biomarker	[26]
Pneumocystis pneumonia	DISFSOM3	Strong	Biomarker	[1]
Sexually transmitted infection	DISIVIAL	Strong	Biomarker	[27]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[28]
Autoimmune disease	DISORMTM	moderate	Biomarker	[29]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[30]
Head and neck cancer	DISBPSQZ	moderate	Biomarker	[31]
Head and neck carcinoma	DISOU1DS	moderate	Biomarker	[31]
HIV infectious disease	DISO97HC	moderate	Genetic Variation	[32]
Stroke	DISX6UHX	moderate	Biomarker	[33]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[34]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[35]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[36]
Immune system disorder	DISAEGPH	Limited	Biomarker	[37]
Malaria	DISQ9Y50	Limited	Biomarker	[38]
Neuralgia	DISWO58J	Limited	Biomarker	[39]
Pancreatic cancer	DISJC981	Limited	Altered Expression	[22]
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⏷ Show the Full List of 49 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Artemin (ARTN) decreases the response to substance of Fulvestrant.	[6]
Camptothecin	DM6CHNJ	Phase 3	Artemin (ARTN) decreases the response to substance of Camptothecin.	[48]
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6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Artemin (ARTN).	[40]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Artemin (ARTN).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Artemin (ARTN).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Artemin (ARTN).	[43]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Artemin (ARTN).	[44]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Artemin (ARTN).	[45]
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⏷ Show the Full List of 6 Drug(s)

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 decreases the methylation of Artemin (ARTN).	[46]
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References

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3	Risk of cancer in children and young adults conceived by assisted reproductive technology.Hum Reprod. 2019 Apr 1;34(4):740-750. doi: 10.1093/humrep/dey394.
4	The Molecular Chaperone Artemin Efficiently Blocks Fibrillization of TAU Protein In Vitro.Cell J. 2018 Jan;19(4):569-577. doi: 10.22074/cellj.2018.4510. Epub 2017 Nov 4.
5	American Heart Association ideal cardiovascular health score and subclinical atherosclerosis in 22-35-year-old adults conceived with and without assisted reproductive technologies.Hum Reprod. 2020 Jan 1;35(1):232-239. doi: 10.1093/humrep/dez240.
6	Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma. Oncogene. 2010 Jun 3;29(22):3228-40. doi: 10.1038/onc.2010.71. Epub 2010 Mar 22.
7	Multicenter fresh frozen tissue sampling in colorectal cancer: does the quality meet the standards for state of the art biomarker research?.Cell Tissue Bank. 2017 Sep;18(3):425-431. doi: 10.1007/s10561-017-9613-x. Epub 2017 Mar 3.
8	Expression and clinical significance of ARTN and MMP-9 in endometrial carcinoma.J Biol Regul Homeost Agents. 2017 Oct-Dec;31(4):879-887.
9	Risk of miscarriage in women with endometriosis undergoing IVF fresh cycles: a retrospective cohort study.Reprod Biol Endocrinol. 2019 Feb 12;17(1):21. doi: 10.1186/s12958-019-0463-1.
10	Relationship Between Vertebral Fractures, Bone Mineral Density, and Osteometabolic Profile in HIV and Hepatitis B and C-Infected Patients Treated With ART.Front Endocrinol (Lausanne). 2019 May 14;10:302. doi: 10.3389/fendo.2019.00302. eCollection 2019.
11	Tumor-Induced Generation of Splenic Erythroblast-like Ter-Cells Promotes Tumor Progression.Cell. 2018 Apr 19;173(3):634-648.e12. doi: 10.1016/j.cell.2018.02.061. Epub 2018 Mar 29.
12	Integrating hypertension screening at the time of voluntary HIV testing among adults in South Africa.PLoS One. 2019 Feb 8;14(2):e0210161. doi: 10.1371/journal.pone.0210161. eCollection 2019.
13	Novel mutations at RET ligand genes preventing receptor activation are associated to Hirschsprung's disease.J Mol Med (Berl). 2011 May;89(5):471-80. doi: 10.1007/s00109-010-0714-2. Epub 2011 Jan 5.
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17	Fertility in adult men born with hypospadias: A nationwide register-based cohort study on birthrates, the use of assisted reproductive technologies and infertility.Andrology. 2020 Mar;8(2):372-380. doi: 10.1111/andr.12723. Epub 2019 Nov 20.
18	Novel therapeutic compound acridine-retrotuftsin action on biological forms of melanoma and neuroblastoma.J Cancer Res Clin Oncol. 2019 Jan;145(1):165-179. doi: 10.1007/s00432-018-2776-4. Epub 2018 Oct 26.
19	Contemporary HCV pangenotypic DAA treatment protocols are exclusionary to real world HIV-HCV co-infected patients.BMC Infect Dis. 2019 May 3;19(1):378. doi: 10.1186/s12879-019-3974-7.
20	miR-223 regulates migration and invasion by targeting Artemin in human esophageal carcinoma.J Biomed Sci. 2011 Mar 31;18(1):24. doi: 10.1186/1423-0127-18-24.
21	Abacavir Use and Risk for Myocardial Infarction and Cardiovascular Events: Pooled Analysis of Data From Clinical Trials.Open Forum Infect Dis. 2018 Apr 20;5(5):ofy086. doi: 10.1093/ofid/ofy086. eCollection 2018 May.
22	Artemin regulates CXCR4 expression to induce migration and invasion in pancreatic cancer cells through activation of NF-B signaling.Exp Cell Res. 2018 Apr 1;365(1):12-23. doi: 10.1016/j.yexcr.2018.02.008. Epub 2018 Feb 14.
23	Tenofovir-associated kidney disease in Africans: a systematic review.AIDS Res Ther. 2019 Jun 6;16(1):12. doi: 10.1186/s12981-019-0227-1.
24	Obesity following ART initiation is common and influenced by both traditional and HIV-/ART-specific risk factors.J Antimicrob Chemother. 2018 Aug 1;73(8):2177-2185. doi: 10.1093/jac/dky145.
25	Does myoinositol supplement improve sperm parameters and DNA integrity in patients with oligoasthenoteratozoospermia after the freezing-thawing process?.Cell Tissue Bank. 2020 Mar;21(1):99-106. doi: 10.1007/s10561-019-09801-7. Epub 2019 Dec 16.
26	Acetyl-L-carnitine increases artemin level and prevents neurotrophic factor alterations during neuropathy.Neuroscience. 2010 Jun 2;167(4):1168-74. doi: 10.1016/j.neuroscience.2010.03.017. Epub 2010 Mar 16.
27	Incidence rate of sexually transmitted infections among HIV infected patients on long-term ART in an urban and a rural clinic in Uganda.BMC Public Health. 2019 Jan 18;19(1):87. doi: 10.1186/s12889-019-6417-x.
28	Quality Control Analysis in Real-time (QC-ART): A Tool for Real-time Quality Control Assessment of Mass Spectrometry-based Proteomics Data.Mol Cell Proteomics. 2018 Sep;17(9):1824-1836. doi: 10.1074/mcp.RA118.000648. Epub 2018 Apr 17.
29	Does subclinical hypothyroidism and/or thyroid autoimmunity influence the IVF/ICSI outcome? Review of the literature.Gynecol Endocrinol. 2019;35(sup1):56-59. doi: 10.1080/09513590.2019.1653564.
30	Plasma glycomics predict cardiovascular disease in patients with ART-controlled HIV infections.FASEB J. 2019 Feb;33(2):1852-1859. doi: 10.1096/fj.201800923R. Epub 2018 Sep 5.
31	Clinical Outcomes of Several IMRT Techniques for Patients With Head and Neck Cancer: A Propensity Score-Weighted Analysis.Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):929-937. doi: 10.1016/j.ijrobp.2017.06.2456. Epub 2017 Jun 27.
32	Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study.J Antimicrob Chemother. 2020 Jan 1;75(1):194-199. doi: 10.1093/jac/dkz424.
33	Computerised mirror therapy with Augmented Reflection Technology for early stroke rehabilitation: clinical feasibility and integration as an adjunct therapy.Disabil Rehabil. 2017 Jul;39(15):1503-1514. doi: 10.1080/09638288.2017.1291765. Epub 2017 Mar 3.
34	A novel MLL-AF10 fusion mRNA variant in a patient with acute myeloid leukemia detected by a new asymmetric reverse transcription PCR method.Leukemia. 1997 Sep;11(9):1588-93. doi: 10.1038/sj.leu.2400758.
35	Prognostic significance of the expression of GFR1, GFR3 and syndecan-3, proteins binding ARTEMIN, in mammary carcinoma.BMC Cancer. 2013 Jan 26;13:34. doi: 10.1186/1471-2407-13-34.
36	Direct-acting Antivirals for HIV/HCV Co-infected Individuals: As Good as it Gets?.Curr HIV Res. 2017;15(6):422-433. doi: 10.2174/1570162X15666171108125255.
37	Strategies for the cure of HIV infection.Enferm Infecc Microbiol Clin (Engl Ed). 2019 Apr;37(4):265-273. doi: 10.1016/j.eimc.2018.01.007. Epub 2018 Mar 3.
38	Artesunate-heparin conjugate based nanocapsules with improved pharmacokinetics to combat malaria.Int J Pharm. 2019 May 1;562:162-171. doi: 10.1016/j.ijpharm.2019.03.031. Epub 2019 Mar 19.
39	Neuropathic pain in HIV patients receiving ART without stavudine in an Indonesia Referral Hospital.J Neurol Sci. 2019 Feb 15;397:146-149. doi: 10.1016/j.jns.2018.12.041. Epub 2019 Jan 2.
40	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
41	Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma. Oncogene. 2010 Jun 3;29(22):3228-40. doi: 10.1038/onc.2010.71. Epub 2010 Mar 22.
42	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.
43	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.
44	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
45	Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
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47	Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma. Oncogene. 2010 Jun 3;29(22):3228-40. doi: 10.1038/onc.2010.71. Epub 2010 Mar 22.
48	ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.