Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJDWX99)

• DOT Name: Enhancer of rudimentary homolog (ERH)
• Gene Name: ERH
• Related Disease:
  Neoplasm
  Hepatocellular carcinoma
  Bladder cancer
  Bladder transitional cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: ERH_HUMAN
• PDB ID: 1W9G; 2NML; 7CNC; 7X39
• Pfam ID: PF01133
• Sequence:
  MSHTILLVQPTKRPEGRTYADYESVNECMEGVCKMYEEHLKRMNPNSPSITYDISQLFDF
  IDDLADLSCLVYRADTQTYQPYNKDWIKEKIYVLLRRQAQQAGK
• Function: May have a role in the cell cycle.
• Tissue Specificity: Expressed in all tissues examined.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]
Bladder cancer	DISUHNM0	Limited	Biomarker	[3]
Bladder transitional cell carcinoma	DISNL46A	Limited	Biomarker	[3]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[3]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Enhancer of rudimentary homolog (ERH).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Enhancer of rudimentary homolog (ERH).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Enhancer of rudimentary homolog (ERH).	[7]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Enhancer of rudimentary homolog (ERH).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of Enhancer of rudimentary homolog (ERH).	[9]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Enhancer of rudimentary homolog (ERH).	[10]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Enhancer of rudimentary homolog (ERH).	[10]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Enhancer of rudimentary homolog (ERH).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Enhancer of rudimentary homolog (ERH).	[11]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Enhancer of rudimentary homolog (ERH).	[12]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Enhancer of rudimentary homolog (ERH).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the ubiquitination of Enhancer of rudimentary homolog (ERH).	[6]

References

• [1] Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells.Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):E3659-67. doi: 10.1073/pnas.1207673110. Epub 2012 Dec 10.
• [2] Enhancer of rudimentary homolog regulates DNA damage response in hepatocellular carcinoma.Sci Rep. 2015 Apr 9;5:9357. doi: 10.1038/srep09357.
• [3] The ERH gene regulates migration and invasion in 5637 and T24 bladder cancer cells.BMC Cancer. 2019 Mar 12;19(1):225. doi: 10.1186/s12885-019-5423-9.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] 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.
• [6] Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome. Chem Res Toxicol. 2022 Sep 19;35(9):1589-1597. doi: 10.1021/acs.chemrestox.2c00197. Epub 2022 Aug 22.
• [7] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [8] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [9] Inhibiting Heat Shock Proteins Can Potentiate the Cytotoxic Effect of Cannabidiol in Human Glioma Cells. Anticancer Res. 2015 Nov;35(11):5827-37.
• [10] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [11] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [12] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [13] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.