Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYQGUB5)

• DOT Name: Interferon beta (IFNB1)
• Synonyms: IFN-beta; Fibroblast interferon
• Gene Name: IFNB1
• UniProt ID: IFNB_HUMAN
• PDB ID: 1AU1
• Pfam ID: PF00143
• Sequence:
  MTNKCLLQIALLLCFSTTALSMSYNLLGFLQRSSNFQCQKLLWQLNGRLEYCLKDRMNFD
  IPEEIKQLQQFQKEDAALTIYEMLQNIFAIFRQDSSSTGWNETIVENLLANVYHQINHLK
  TVLEEKLEKEDFTRGKLMSSLHLKRYYGRILHYLKAKEYSHCAWTIVRVEILRNFYFINR
  LTGYLRN
• Function: Type I interferon cytokine that plays a key role in the innate immune response to infection, developing tumors and other inflammatory stimuli. Signals via binding to high-affinity (IFNAR2) and low-affinity (IFNAR1) heterodimeric receptor, activating the canonical Jak-STAT signaling pathway resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response, such as antiviral proteins, regulators of cell proliferation and differentiation, and immunoregulatory proteins. Signals mostly via binding to a IFNAR1-IFNAR2 heterodimeric receptor, but can also function with IFNAR1 alone and independently of Jak-STAT pathways. Elicits a wide variety of responses, including antiviral and antibacterial activities, and can regulate the development of B-cells, myelopoiesis and lipopolysaccharide (LPS)-inducible production of tumor necrosis factor. Plays a role in neuronal homeostasis by regulating dopamine turnover and protecting dopaminergic neurons: acts by promoting neuronal autophagy and alpha-synuclein clearance, thereby preventing dopaminergic neuron loss. IFNB1 is more potent than interferon-alpha (IFN-alpha) in inducing the apoptotic and antiproliferative pathways required for control of tumor cell growth.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  Necroptosis (hsa04217)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor sig.ling pathway (hsa04620)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  Cytosolic D.-sensing pathway (hsa04623)
  JAK-STAT sig.ling pathway (hsa04630)
  .tural killer cell mediated cytotoxicity (hsa04650)
  TNF sig.ling pathway (hsa04668)
  Alcoholic liver disease (hsa04936)
  Shigellosis (hsa05131)
  Yersinia infection (hsa05135)
  Chagas disease (hsa05142)
  Tuberculosis (hsa05152)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Coro.virus disease - COVID-19 (hsa05171)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Interferon alpha/beta signaling (R-HSA-909733)
  Regulation of IFNA/IFNB signaling (R-HSA-912694)
  TRAF3-dependent IRF activation pathway (R-HSA-918233)
  TRAF6 mediated IRF7 activation (R-HSA-933541)
  SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  Oxidative Stress Induced Senescence (R-HSA-2559580)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Interferon beta (IFNB1) increases the response to substance of Fluorouracil.	[10]
Mitotane	DMU1GX0	Approved	Interferon beta (IFNB1) increases the response to substance of Mitotane.	[11]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydrocortisone	DMGEMB7	Approved	Interferon beta (IFNB1) decreases the secretion of Hydrocortisone.	[11]

9 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 Interferon beta (IFNB1).	[1]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Interferon beta (IFNB1).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Interferon beta (IFNB1).	[3]
Hydroxychloroquine	DMSIVND	Approved	Hydroxychloroquine increases the expression of Interferon beta (IFNB1).	[4]
Aripiprazole	DM3NUMH	Approved	Aripiprazole increases the expression of Interferon beta (IFNB1).	[5]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Interferon beta (IFNB1).	[6]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 increases the expression of Interferon beta (IFNB1).	[7]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Interferon beta (IFNB1).	[8]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of Interferon beta (IFNB1).	[9]

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] 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.
• [3] STAT-1 signaling in human lung fibroblasts is induced by vanadium pentoxide through an IFN-beta autocrine loop. J Immunol. 2008 Mar 15;180(6):4200-7. doi: 10.4049/jimmunol.180.6.4200.
• [4] Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
• [5] Small Molecule Antipsychotic Aripiprazole Potentiates Ozone-Induced Inflammation in Airway Epithelium. Chem Res Toxicol. 2019 Oct 21;32(10):1997-2005. doi: 10.1021/acs.chemrestox.9b00149. Epub 2019 Sep 11.
• [6] 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.
• [7] Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule inhibitor that targets p21-activated kinase 4. Oncol Rep. 2017 Nov;38(5):2705-2716. doi: 10.3892/or.2017.5989. Epub 2017 Sep 22.
• [8] Gas-inducible product gene expression in bioreactors. Metab Eng. 2005 May;7(3):174-81. doi: 10.1016/j.ymben.2005.01.003.
• [9] Microcystin-LR-induced nuclear translocation of cGAS promotes mutagenesis in human hepatocytes by impeding homologous recombination repair. Toxicol Lett. 2023 Jan 15;373:94-104. doi: 10.1016/j.toxlet.2022.11.015. Epub 2022 Nov 23.
• [10] Interferons upregulate thymidine phosphorylase expression via JAK-STAT-dependent transcriptional activation and mRNA stabilization in human glioblastoma cells. J Neurooncol. 2005 May;72(3):217-23. doi: 10.1007/s11060-004-3012-4.
• [11] Interferon- is a potent inhibitor of cell growth and cortisol production in vitro and sensitizes human adrenocortical carcinoma cells to mitotane. Endocr Relat Cancer. 2013 May 30;20(3):443-54. doi: 10.1530/ERC-12-0217. Print 2013 Jun.