Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8M3H72)

• DOT Name: Fibroleukin (FGL2)
• Synonyms: Fibrinogen-like protein 2; pT49
• Gene Name: FGL2
• UniProt ID: FGL2_HUMAN
• Pfam ID: PF00147
• Sequence:
  MKLANWYWLSSAVLATYGFLVVANNETEEIKDERAKDVCPVRLESRGKCEEAGECPYQVS
  LPPLTIQLPKQFSRIEEVFKEVQNLKEIVNSLKKSCQDCKLQADDNGDPGRNGLLLPSTG
  APGEVGDNRVRELESEVNKLSSELKNAKEEINVLHGRLEKLNLVNMNNIENYVDSKVANL
  TFVVNSLDGKCSKCPSQEQIQSRPVQHLIYKDCSDYYAIGKRSSETYRVTPDPKNSSFEV
  YCDMETMGGGWTVLQARLDGSTNFTRTWQDYKAGFGNLRREFWLGNDKIHLLTKSKEMIL
  RIDLEDFNGVELYALYDQFYVANEFLKYRLHVGNYNGTAGDALRFNKHYNHDLKFFTTPD
  KDNDRYPSGNCGLYYSSGWWFDACLSANLNGKYYHQKYRGVRNGIFWGTWPGVSEAHPGG
  YKSSFKEAKMMIRPKHFKP
• Function: May play a role in physiologic lymphocyte functions at mucosal sites.
• Tissue Specificity: Constitutively expressed in cytotoxic T-cells.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Fibroleukin (FGL2).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Fibroleukin (FGL2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Fibroleukin (FGL2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Fibroleukin (FGL2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fibroleukin (FGL2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Fibroleukin (FGL2).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Fibroleukin (FGL2).	[8]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Fibroleukin (FGL2).	[9]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Fibroleukin (FGL2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fibroleukin (FGL2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fibroleukin (FGL2).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Fibroleukin (FGL2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Fibroleukin (FGL2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Fibroleukin (FGL2).	[11]

References

• [1] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] 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.
• [4] Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders. J Mol Endocrinol. 2015 Jun;54(3):289-303.
• [5] Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014 May;9(5):774-82. doi: 10.4161/epi.28153. Epub 2014 Feb 13.
• [6] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [7] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [10] Microarray analyses in dendritic cells reveal potential biomarkers for chemical-induced skin sensitization. Mol Immunol. 2007 May;44(12):3222-33.
• [11] 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.
• [12] Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
• [13] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.