Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1TP2T8)

• DOT Name: Cerebral dopamine neurotrophic factor (CDNF)
• Synonyms: ARMET-like protein 1; Conserved dopamine neurotrophic factor
• Gene Name: CDNF
• Related Disease:
  Nervous system disease
  Alzheimer disease
  Cerebral infarction
  Parkinson disease
  Schizophrenia
  Stroke
  Type-1/2 diabetes
• UniProt ID: CDNF_HUMAN
• PDB ID: 2LPN; 2W50; 4BIT
• Pfam ID: PF10208 ; PF20145
• Sequence:
  MWCASPVAVVAFCAGLLVSHPVLTQGQEAGGRPGADCEVCKEFLNRFYKSLIDRGVNFSL
  DTIEKELISFCLDTKGKENRLCYYLGATKDAATKILSEVTRPMSVHMPAMKICEKLKKLD
  SQICELKYEKTLDLASVDLRKMRVAELKQILHSWGEECRACAEKTDYVNLIQELAPKYAA
  THPKTEL
• Function: Trophic factor for dopamine neurons. Prevents the 6-hydroxydopamine (6-OHDA)-induced degeneration of dopaminergic neurons. When administered after 6-OHDA-lesioning, restores the dopaminergic function and prevents the degeneration of dopaminergic neurons in substantia nigra.
• Tissue Specificity: Widely expressed in neuronal and non-neuronal tissues. In the brain, highest levels in the optic nerve and corpus callosum.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nervous system disease	DISJ7GGT	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Cerebral infarction	DISR1WNP	Strong	Altered Expression	[3]
Parkinson disease	DISQVHKL	Strong	Biomarker	[4]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[5]
Stroke	DISX6UHX	Strong	Altered Expression	[6]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Cerebral dopamine neurotrophic factor (CDNF).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cerebral dopamine neurotrophic factor (CDNF).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cerebral dopamine neurotrophic factor (CDNF).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cerebral dopamine neurotrophic factor (CDNF).	[11]

References

• [1] Neuroprotective and reparative effects of endoplasmic reticulum luminal proteins - mesencephalic astrocyte-derived neurotrophic factor and cerebral dopamine neurotrophic factor.Croat Med J. 2019 Apr 30;60(2):99-108. doi: 10.3325/cmj.2019.60.99.
• [2] Characterization of CDNF-Secreting ARPE-19 Cell Clones for Encapsulated Cell Therapy.Cell Transplant. 2019 Apr;28(4):413-424. doi: 10.1177/0963689719827943. Epub 2019 Mar 6.
• [3] Cerebral Dopamine Neurotrophic Factor (CDNF) Has Neuroprotective Effects against Cerebral Ischemia That May Occur through the Endoplasmic Reticulum Stress Pathway.Int J Mol Sci. 2018 Jun 29;19(7):1905. doi: 10.3390/ijms19071905.
• [4] Cerebral dopamine neurotrophic factor-deficiency leads to degeneration of enteric neurons and altered brain dopamine neuronal function in mice.Neurobiol Dis. 2020 Feb;134:104696. doi: 10.1016/j.nbd.2019.104696. Epub 2019 Nov 26.
• [5] Association between cerebral dopamine neurotrophic factor (CDNF) 2 polymorphisms and schizophrenia susceptibility and symptoms in the Han Chinese population.Behav Brain Funct. 2018 Jan 3;14(1):1. doi: 10.1186/s12993-017-0133-4.
• [6] Decreased Expression of Cerebral Dopamine Neurotrophic Factor in Platelets of Stroke Patients.J Stroke Cerebrovasc Dis. 2020 Jan;29(1):104502. doi: 10.1016/j.jstrokecerebrovasdis.2019.104502. Epub 2019 Nov 16.
• [7] Unconventional neurotrophic factors CDNF and MANF: Structure, physiological functions and therapeutic potential.Neurobiol Dis. 2017 Jan;97(Pt B):90-102. doi: 10.1016/j.nbd.2016.07.009. Epub 2016 Jul 15.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.