Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR1JN1D)

• DOT Name: Glia maturation factor beta (GMFB)
• Synonyms: GMF-beta
• Gene Name: GMFB
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Neoplasm
  Alzheimer disease
  Schizophrenia
  Encephalitis
• UniProt ID: GMFB_HUMAN
• Pfam ID: PF00241
• Sequence:
  MSESLVVCDVAEDLVEKLRKFRFRKETNNAAIIMKIDKDKRLVVLDEELEGISPDELKDE
  LPERQPRFIVYSYKYQHDDGRVSYPLCFIFSSPVGCKPEQQMMYAGSKNKLVQTAELTKV
  FEIRNTEDLTEEWLREKLGFFH
• Function: This protein causes differentiation of brain cells, stimulation of neural regeneration, and inhibition of proliferation of tumor cells.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Encephalitis	DISLD1RL	moderate	Altered Expression	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Glia maturation factor beta (GMFB).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glia maturation factor beta (GMFB).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glia maturation factor beta (GMFB).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glia maturation factor beta (GMFB).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Glia maturation factor beta (GMFB).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Glia maturation factor beta (GMFB).	[11]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glia maturation factor beta (GMFB).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Glia maturation factor beta (GMFB).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Glia maturation factor beta (GMFB).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Glia maturation factor beta (GMFB).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Glia maturation factor beta (GMFB).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glia maturation factor beta (GMFB).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glia maturation factor beta (GMFB).	[18]

References

• [1] -Elemene inhibits proliferation through crosstalk between glia maturation factor and extracellular signalregulated kinase1/2 and impairs drug resistance to temozolomide in glioblastoma cells.Mol Med Rep. 2014 Aug;10(2):1122-8. doi: 10.3892/mmr.2014.2273. Epub 2014 May 27.
• [2] -elemene inhibits proliferation of human glioblastoma cells through the activation of glia maturation factor and induces sensitization to cisplatin.Oncol Rep. 2011 Aug;26(2):405-13. doi: 10.3892/or.2011.1276. Epub 2011 Apr 20.
• [3] Targeted Gene Editing of Glia Maturation Factor in Microglia: a Novel Alzheimer's Disease Therapeutic Target.Mol Neurobiol. 2019 Jan;56(1):378-393. doi: 10.1007/s12035-018-1068-y. Epub 2018 Apr 27.
• [4] Proteomics in Schizophrenia: A Gateway to Discover Potential Biomarkers of Psychoneuroimmune Pathways.Front Psychiatry. 2019 Nov 29;10:885. doi: 10.3389/fpsyt.2019.00885. eCollection 2019.
• [5] First description of enhanced expression of glia maturation factor-beta in experimental toxoplasmic encephalitis.J Int Med Res. 2017 Dec;45(6):1670-1679. doi: 10.1177/0300060517700320. Epub 2017 Aug 4.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] 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.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [17] 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.
• [18] 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.