Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4GII73)

• DOT Name: Interferon alpha-2 (IFNA2)
• Synonyms: IFN-alpha-2; Interferon alpha-A; LeIF A
• Gene Name: IFNA2
• UniProt ID: IFNA2_HUMAN
• PDB ID: 1ITF; 1RH2; 2HYM; 2KZ1; 2LAG; 2LMS; 3S9D; 3SE3; 4YPG; 4Z5R
• Pfam ID: PF00143
• Sequence:
  MALTFALLVALLVLSCKSSCSVGCDLPQTHSLGSRRTLMLLAQMRRISLFSCLKDRHDFG
  FPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEA
  CVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNL
  QESLRSKE
• Function: Produced by macrophages, IFN-alpha have antiviral activities.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt sig.ling pathway (hsa04151)
  Necroptosis (hsa04217)
  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)
  Alcoholic liver disease (hsa04936)
  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)
  Pathways in cancer (hsa05200)
  Autoimmune thyroid disease (hsa05320)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Regulation of IFNA/IFNB signaling (R-HSA-912694)
  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)
  Interferon alpha/beta signaling (R-HSA-909733)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Interferon alpha-2 (IFNA2).	[1]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Interferon alpha-2 (IFNA2).	[2]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Interferon alpha-2 (IFNA2).	[2]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Interferon alpha-2 (IFNA2).	[3]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 increases the expression of Interferon alpha-2 (IFNA2).	[4]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
BIX-01294	DM5CBNY	Preclinical	BIX-01294 increases the response to substance of Interferon alpha-2 (IFNA2).	[5]
UNC0638	DM4A1KJ	Investigative	UNC0638 increases the response to substance of Interferon alpha-2 (IFNA2).	[5]

References

• [1] 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.
• [2] Progesterone and calcitriol attenuate inflammatory cytokines CXCL1 and CXCL2 in ovarian and endometrial cancer cells. J Cell Biochem. 2012 Oct;113(10):3143-52. doi: 10.1002/jcb.24191.
• [3] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [4] 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.
• [5] Inhibition of euchromatic histone methyltransferase 1 and 2 sensitizes chronic myeloid leukemia cells to interferon treatment. PLoS One. 2014 Jul 31;9(7):e103915. doi: 10.1371/journal.pone.0103915. eCollection 2014.