Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5JW5RB)

• DOT Name: Mammalian ependymin-related protein 1 (EPDR1)
• Synonyms: MERP-1; Upregulated in colorectal cancer gene 1 protein
• Gene Name: EPDR1
• Related Disease:
  Alzheimer disease
  Angle-closure glaucoma
  Colorectal carcinoma
  Primary angle-closure glaucoma
• UniProt ID: EPDR1_HUMAN
• PDB ID: 6E7O; 6E8N; 6JLD
• Pfam ID: PF00811
• Sequence:
  MPGRAPLRTVPGALGAWLLGGLWAWTLCGLCSLGAVGAPRPCQAPQQWEGRQVMYQQSSG
  RNSRALLSYDGLNQRVRVLDERKALIPCKRLFEYILLYKDGVMFQIDQATKQCSKMTLTQ
  PWDPLDIPQNSTFEDQYSIGGPQEQITVQEWSDRKSARSYETWIGIYTVKDCYPVQETFT
  INYSVILSTRFFDIQLGIKDPSVFTPPSTCQMAQLEKMSEDCSW
• Function: Binds anionic lipids and gangliosides at acidic pH.
• Tissue Specificity: Ubiquitous. Detected in brain, heart, skeletal muscle, kidney, testis, ovary and prostate.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Angle-closure glaucoma	DISZ95KY	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[3]
Primary angle-closure glaucoma	DISX8UKZ	moderate	Genetic Variation	[2]

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 Mammalian ependymin-related protein 1 (EPDR1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[7]
Marinol	DM70IK5	Approved	Marinol increases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[8]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[9]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[13]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Mammalian ependymin-related protein 1 (EPDR1).	[14]

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 Mammalian ependymin-related protein 1 (EPDR1).	[11]

References

• [1] Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk.Nat Genet. 2019 Mar;51(3):404-413. doi: 10.1038/s41588-018-0311-9. Epub 2019 Jan 7.
• [2] Integration of Genetic and Biometric Risk Factors for Detection of Primary Angle Closure Glaucoma.Am J Ophthalmol. 2019 Dec;208:160-165. doi: 10.1016/j.ajo.2019.07.022. Epub 2019 Aug 1.
• [3] Prognostic Values of EPDR1 Hypermethylation and Its Inhibitory Function on Tumor Invasion in Colorectal Cancer.Cancers (Basel). 2018 Oct 22;10(10):393. doi: 10.3390/cancers10100393.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S. Toxicol In Vitro. 2015 Aug;29(5):1060-9.
• [14] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.