Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCDL9PG)

• DOT Name: Protein NDNF (NDNF)
• Synonyms: Neuron-derived neurotrophic factor
• Gene Name: NDNF
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Germ cell tumor
  Hypogonadotropic hypogonadism 25 with anosmia
  Myocardial infarction
  Vascular disease
  Kallmann syndrome
  Endometriosis
  Clear cell renal carcinoma
  Renal cell carcinoma
• UniProt ID: NDNF_HUMAN
• Pfam ID: PF10179 ; PF19433
• Sequence:
  MVLLHWCLLWLLFPLSSRTQKLPTRDEELFQMQIRDKAFFHDSSVIPDGAEISSYLFRDT
  PKRYFFVVEEDNTPLSVTVTPCDAPLEWKLSLQELPEDRSGEGSGDLEPLEQQKQQIINE
  EGTELFSYKGNDVEYFISSSSPSGLYQLDLLSTEKDTHFKVYATTTPESDQPYPELPYDP
  RVDVTSLGRTTVTLAWKPSPTASLLKQPIQYCVVINKEHNFKSLCAVEAKLSADDAFMMA
  PKPGLDFSPFDFAHFGFPSDNSGKERSFQAKPSPKLGRHVYSRPKVDIQKICIGNKNIFT
  VSDLKPDTQYYFDVFVVNINSNMSTAYVGTFARTKEEAKQKTVELKDGKITDVFVKRKGA
  KFLRFAPVSSHQKVTFFIHSCLDAVQIQVRRDGKLLLSQNVEGIQQFQLRGKPKAKYLVR
  LKGNKKGASMLKILATTRPTKQSFPSLPEDTRIKAFDKLRTCSSATVAWLGTQERNKFCI
  YKKEVDDNYNEDQKKREQNQCLGPDIRKKSEKVLCKYFHSQNLQKAVTTETIKGLQPGKS
  YLLDVYVIGHGGHSVKYQSKVVKTRKFC
• Function: Secretory protein that plays a role in various cellular processes. Acts as a chemorepellent acting on gonadotropin-releasing hormone (GnRH) expressing neurons regulating their migration to the hypothalamus. Also promotes neuron migration, growth and survival as well as neurite outgrowth and is involved in the development of the olfactory system. May also act through the regulation of growth factors activity and downstream signaling. Also regulates extracellular matrix assembly and cell adhesiveness. Promotes endothelial cell survival, vessel formation and plays an important role in the process of revascularization through NOS3-dependent mechanisms.
• Tissue Specificity: Expressed in neurons along the gonadotropin-releasing hormone (GnRH) expressing neurons migratory route.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[1]
Germ cell tumor	DIS62070	Strong	Biomarker	[2]
Hypogonadotropic hypogonadism 25 with anosmia	DIS50EIZ	Strong	Autosomal dominant	[3]
Myocardial infarction	DIS655KI	Strong	Biomarker	[4]
Vascular disease	DISVS67S	Strong	Biomarker	[5]
Kallmann syndrome	DISO3HDG	Supportive	Autosomal dominant	[3]
Endometriosis	DISX1AG8	Disputed	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[7]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[7]

8 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 Protein NDNF (NDNF).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein NDNF (NDNF).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein NDNF (NDNF).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein NDNF (NDNF).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Protein NDNF (NDNF).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein NDNF (NDNF).	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Protein NDNF (NDNF).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein NDNF (NDNF).	[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 increases the methylation of Protein NDNF (NDNF).	[14]

References

• [1] Long noncoding RNA BDNF-AS is downregulated in cervical cancer and has anti-cancer functions by negatively associating with BDNF.Arch Biochem Biophys. 2018 May 15;646:113-119. doi: 10.1016/j.abb.2018.03.023. Epub 2018 Mar 21.
• [2] Parental Occupational Exposure to Organic Solvents and Testicular Germ Cell Tumors in their Offspring: NORD-TEST Study.Environ Health Perspect. 2017 Jun 30;125(6):067023. doi: 10.1289/EHP864.
• [3] Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism. Am J Hum Genet. 2020 Jan 2;106(1):58-70. doi: 10.1016/j.ajhg.2019.12.003. Epub 2019 Dec 26.
• [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] Neuron-derived neurotrophic factor functions as a novel modulator that enhances endothelial cell function and revascularization processes.J Biol Chem. 2014 May 16;289(20):14132-44. doi: 10.1074/jbc.M114.555789. Epub 2014 Apr 6.
• [6] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [7] NDNF inhibits the migration and invasion of human renal cancer cells through epithelial-mesenchymal transition.Oncol Lett. 2019 Mar;17(3):2969-2975. doi: 10.3892/ol.2019.9937. Epub 2019 Jan 15.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] 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.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] 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.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [14] 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.
• [15] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.