Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGL7MHB)

• DOT Name: Neudesin (NENF)
• Synonyms: Cell immortalization-related protein 2; Neuron-derived neurotrophic factor; Protein GIG47; Secreted protein of unknown function; SPUF protein
• Gene Name: NENF
• Related Disease:
  Type-1 diabetes
  Type-1/2 diabetes
  Liver cirrhosis
  Meningioma tumour
  Myocardial infarction
• UniProt ID: NENF_HUMAN
• Pfam ID: PF00173
• Sequence:
  MVGPAPRRRLRPLAALALVLALAPGLPTARAGQTPRPAERGPPVRLFTEEELARYGGEEE
  DQPIYLAVKGVVFDVTSGKEFYGRGAPYNALTGKDSTRGVAKMSLDPADLTHDTTGLTAK
  ELEALDEVFTKVYKAKYPIVGYTARRILNEDGSPNLDFKPEDQPHFDIKDEF
• Function: Acts as a neurotrophic factor in postnatal mature neurons enhancing neuronal survival. Promotes cell proliferation and neurogenesis in undifferentiated neural progenitor cells at the embryonic stage and inhibits differentiation of astrocytes. Its neurotrophic activity is exerted via MAPK1/ERK2, MAPK3/ERK1 and AKT1/AKT pathways. Neurotrophic activity is enhanced by binding to heme. Acts also as an anorexigenic neurotrophic factor that contributes to energy balance.
• Tissue Specificity: Ubiquitously expressed with high expression in heart. Over-expressed in various tumors including carcinomas of the uterine cervix, lymphoma, colon, lung, skin and leukemia, as well as carcinoma of the breast.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Type-1 diabetes	DIS7HLUB	Definitive	Altered Expression	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[1]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[2]
Meningioma tumour	DISOZOR8	Strong	Biomarker	[3]
Myocardial infarction	DIS655KI	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Neudesin (NENF).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Neudesin (NENF).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Neudesin (NENF).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neudesin (NENF).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Neudesin (NENF).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Neudesin (NENF).	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Neudesin (NENF).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neudesin (NENF).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neudesin (NENF).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Neudesin (NENF).	[15]

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 affects the methylation of Neudesin (NENF).	[12]

References

• [1] Assessment of Serum Concentrations of Adropin, Afamin, and Neudesin in Children with Type 1 Diabetes.Biomed Res Int. 2019 Oct 24;2019:6128410. doi: 10.1155/2019/6128410. eCollection 2019.
• [2] Effect of Different Circuit Training on Cardiovascular Responses in Cirrhotic Patients.Int J Sports Med. 2019 Feb;40(2):139-146. doi: 10.1055/a-0783-2747. Epub 2018 Dec 17.
• [3] Serum and cerebrospinal fluid Neudesin concentration and Neudesin Quotient as potential circulating biomarkers of a primary brain tumor.BMC Cancer. 2019 Apr 5;19(1):319. doi: 10.1186/s12885-019-5525-4.
• [4] Effect of neuron-derived neurotrophic factor on rejuvenation of human adipose-derived stem cells for cardiac repair after myocardial infarction.J Cell Mol Med. 2019 Sep;23(9):5981-5993. doi: 10.1111/jcmm.14456. Epub 2019 Jul 9.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] 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.
• [13] 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.
• [14] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.