Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVE05K7)

• DOT Name: Melanoma-associated antigen H1 (MAGEH1)
• Synonyms: Apoptosis-related protein 1; APR-1; MAGE-H1 antigen; Restin
• Gene Name: MAGEH1
• Related Disease:
  Classic Hodgkin lymphoma
  Advanced cancer
  Anaplastic large cell lymphoma
  Cholangiocarcinoma
  Familial adenomatous polyposis
  Neoplasm
  Pancreatic cancer
  Melanoma
  Breast cancer
  Breast carcinoma
  Metastatic malignant neoplasm
  Hepatocellular carcinoma
• UniProt ID: MAGH1_HUMAN
• Pfam ID: PF01454
• Sequence:
  MPRGRKSRRRRNARAAEENRNNRKIQASEASETPMAASVVASTPEDDLSGPEEDPSTPEE
  ASTTPEEASSTAQAQKPSVPRSNFQGTKKSLLMSILALIFIMGNSAKEALVWKVLGKLGM
  QPGRQHSIFGDPKKIVTEEFVRRGYLIYKPVPRSSPVEYEFFWGPRAHVESSKLKVMHFV
  ARVRNRCSKDWPCNYDWDSDDDAEVEAILNSGARGYSAP

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Altered Expression	[3]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[2]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[5]
Melanoma	DIS1RRCY	moderate	Biomarker	[6]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[7]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Altered Expression	[7]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Melanoma-associated antigen H1 (MAGEH1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Melanoma-associated antigen H1 (MAGEH1).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Melanoma-associated antigen H1 (MAGEH1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Melanoma-associated antigen H1 (MAGEH1).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Melanoma-associated antigen H1 (MAGEH1).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Melanoma-associated antigen H1 (MAGEH1).	[13]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Melanoma-associated antigen H1 (MAGEH1).	[14]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Melanoma-associated antigen H1 (MAGEH1).	[15]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Melanoma-associated antigen H1 (MAGEH1).	[16]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Melanoma-associated antigen H1 (MAGEH1).	[17]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Melanoma-associated antigen H1 (MAGEH1).	[19]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Melanoma-associated antigen H1 (MAGEH1).	[20]

References

• [1] Hodgkin and Reed-Sternberg cell-associated autoantigen CLIP-170/restin is a marker for dendritic cells and is involved in the trafficking of macropinosomes to the cytoskeleton, supporting a function-based concept of Hodgkin and Reed-Sternberg cells.Blood. 2002 Dec 1;100(12):4139-45. doi: 10.1182/blood.V100.12.4139.
• [2] Apoptosis-related protein-1 acts as a tumor suppressor in cholangiocarcinoma cells by inducing cell cycle arrest via downregulation of cyclin-dependent kinase subunits.Oncol Rep. 2016 Feb;35(2):809-16. doi: 10.3892/or.2015.4422. Epub 2015 Nov 16.
• [3] Restin in Hodgkin's disease and anaplastic large cell lymphoma.Leuk Lymphoma. 1993 Dec;12(1-2):21-6. doi: 10.3109/10428199309059567.
• [4] Tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans asymmetric cell division.Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E954-E963. doi: 10.1073/pnas.1712052115. Epub 2018 Jan 18.
• [5] Reversion of multidrug resistance in the P-glycoprotein-positive human pancreatic cell line (EPP85-181RDB) by introduction of a hammerhead ribozyme.Br J Cancer. 1994 Aug;70(2):239-43. doi: 10.1038/bjc.1994.286.
• [6] Apoptosis related protein-1 triggers melanoma cell death via interaction with the juxtamembrane region of p75 neurotrophin receptor.J Cell Mol Med. 2012 Feb;16(2):349-61. doi: 10.1111/j.1582-4934.2011.01304.x.
• [7] Restin suppressed epithelial-mesenchymal transition and tumor metastasis in breast cancer cells through upregulating mir-200a/b expression via association with p73.Mol Cancer. 2015 May 14;14:102. doi: 10.1186/s12943-015-0370-9.
• [8] Downregulation of MAGE family member H1 enhances hepatocellular carcinoma progression and serves as a biomarker for patient prognosis.Future Oncol. 2018 May;14(12):1177-1186. doi: 10.2217/fon-2017-0672. Epub 2018 Jan 10.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [15] 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.
• [16] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [17] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [18] 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.
• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [20] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.