Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG5FN5S)

• DOT Name: Melanoma-derived growth regulatory protein (MIA)
• Synonyms: Melanoma inhibitory activity protein
• Gene Name: MIA
• UniProt ID: MIA_HUMAN
• PDB ID: 1HJD; 1I1J; 1K0X; 5IXB
• Pfam ID: PF07653
• Sequence:
  MARSLVCLGVIILLSAFSGPGVRGGPMPKLADRKLCADQECSHPISMAVALQDYMAPDCR
  FLTIHRGQVVYVFSKLKGRGRLFWGGSVQGDYYGDLAARLGYFPSSIVREDQTLKPGKVD
  VKTDKWDFYCQ
• Function: Elicits growth inhibition on melanoma cells in vitro as well as some other neuroectodermal tumors, including gliomas.
• Tissue Specificity: All malignant melanoma cell lines tested and infrequently in glioma cell lines.

Molecular Interaction Atlas (MIA) of This DOT

11 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 Melanoma-derived growth regulatory protein (MIA).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Melanoma-derived growth regulatory protein (MIA).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Melanoma-derived growth regulatory protein (MIA).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Melanoma-derived growth regulatory protein (MIA).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Melanoma-derived growth regulatory protein (MIA).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Melanoma-derived growth regulatory protein (MIA).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Melanoma-derived growth regulatory protein (MIA).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Melanoma-derived growth regulatory protein (MIA).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the expression of Melanoma-derived growth regulatory protein (MIA).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Melanoma-derived growth regulatory protein (MIA).	[11]
Manganese	DMKT129	Investigative	Manganese increases the expression of Melanoma-derived growth regulatory protein (MIA).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Melanoma-derived growth regulatory protein (MIA).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Melanoma-derived growth regulatory protein (MIA).	[10]

References

• [1] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
• [6] 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.
• [7] Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther. 2013 Feb;27(1):37-48. doi: 10.1007/s10557-012-6427-8.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.