Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI2645G)

• DOT Name: Meteorin (METRN)
• Gene Name: METRN
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Coronary atherosclerosis
  Coronary heart disease
  Huntington disease
  Malignant mesothelioma
  Obesity
  Nervous system disease
  Non-insulin dependent diabetes
• UniProt ID: METRN_HUMAN
• Sequence:
  MGFPAAALLCALCCGLLAPAARAGYSEERCSWRGSGLTQEPGSVGQLALACAEGAVEWLY
  PAGALRLTLGGPDPRARPGIACLRPVRPFAGAQVFAERAGGALELLLAEGPGPAGGRCVR
  WGPRERRALFLQATPHQDISRRVAAFRFELREDGRPELPPQAHGLGVDGACRPCSDAELL
  LAACTSDFVIHGIIHGVTHDVELQESVITVVAARVLRQTPPLFQAGRSGDQGLTSIRTPL
  RCGVHPGPGTFLFMGWSRFGEARLGCAPRFQEFRRAYEAARAAHLHPCEVALH
• Function: Involved in both glial cell differentiation and axonal network formation during neurogenesis. Promotes astrocyte differentiation and transforms cerebellar astrocytes into radial glia. Also induces axonal extension in small and intermediate neurons of sensory ganglia by activating nearby satellite glia.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Coronary atherosclerosis	DISKNDYU	Strong	Altered Expression	[2]
Coronary heart disease	DIS5OIP1	Strong	Altered Expression	[2]
Huntington disease	DISQPLA4	Strong	Biomarker	[3]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[4]
Obesity	DIS47Y1K	Strong	Altered Expression	[5]
Nervous system disease	DISJ7GGT	Limited	Biomarker	[6]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Meteorin (METRN).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Meteorin (METRN).	[16]

11 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 Meteorin (METRN).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Meteorin (METRN).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Meteorin (METRN).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Meteorin (METRN).	[12]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Meteorin (METRN).	[13]
Exemestane	DM9HPW3	Approved	Exemestane increases the expression of Meteorin (METRN).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Meteorin (METRN).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Meteorin (METRN).	[17]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of Meteorin (METRN).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Meteorin (METRN).	[18]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Meteorin (METRN).	[19]

References

• [1] Association of low serum Meteorin like (Metrnl) concentrations with worsening of glucose tolerance, impaired endothelial function and atherosclerosis.Diabetes Res Clin Pract. 2019 Apr;150:57-63. doi: 10.1016/j.diabres.2019.02.026. Epub 2019 Feb 27.
• [2] Lower serum levels of Meteorin-like/Subfatin in patients with coronary artery disease and type 2 diabetes mellitus are negatively associated with insulin resistance and inflammatory cytokines.PLoS One. 2018 Sep 13;13(9):e0204180. doi: 10.1371/journal.pone.0204180. eCollection 2018.
• [3] Encapsulated cell-based biodelivery of meteorin is neuroprotective in the quinolinic acid rat model of neurodegenerative disease.Restor Neurol Neurosci. 2012;30(3):225-36. doi: 10.3233/RNN-2012-110199.
• [4] Can novel adipokines, asprosin and meteorin-like, be biomarkers for malignant mesothelioma?.Biotech Histochem. 2020 Apr;95(3):171-175. doi: 10.1080/10520295.2019.1656344. Epub 2019 Oct 1.
• [5] Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin.Cells. 2019 Oct 19;8(10):1283. doi: 10.3390/cells8101283.
• [6] Lentiviral delivery of meteorin protects striatal neurons against excitotoxicity and reverses motor deficits in the quinolinic acid rat model.Neurobiol Dis. 2011 Jan;41(1):160-8. doi: 10.1016/j.nbd.2010.09.003. Epub 2010 Sep 16.
• [7] Serum Levels of Meteorin-Like (Metrnl) Are Increased in Patients with Newly Diagnosed Type 2 Diabetes Mellitus and Are Associated with Insulin Resistance.Med Sci Monit. 2019 Mar 31;25:2337-2343. doi: 10.12659/MSM.915331.
• [8] 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.
• [9] 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.
• [10] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [14] Effects of aromatase inhibitors on human osteoblast and osteoblast-like cells: a possible androgenic bone protective effects induced by exemestane. Bone. 2007 Apr;40(4):876-87. doi: 10.1016/j.bone.2006.11.029. Epub 2006 Dec 28.
• [15] 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.
• [16] 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.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.