Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPMKY0L)

DOT Name	Interferon alpha-1/13 (IFNA1)
Synonyms	IFN-alpha-1/13; Interferon alpha-D; LeIF D
Gene Name	IFNA1
Related Disease	Tuberculosis ( ) Acquired immune deficiency syndrome ( ) Acute lymphocytic leukaemia ( ) Adenocarcinoma ( ) Adult glioblastoma ( ) Adult T-cell leukemia/lymphoma ( ) Anemia ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Bacterial infection ( ) Bipolar disorder ( ) Breast cancer ( ) Breast carcinoma ( ) Clear cell renal carcinoma ( ) Colorectal carcinoma ( ) Colorectal neoplasm ( ) Dermatomyositis ( ) Glioblastoma multiforme ( ) Hepatitis A virus infection ( ) Lung cancer ( ) Lung carcinoma ( ) Major depressive disorder ( ) Multiple sclerosis ( ) Nervous system inflammation ( ) Neuroblastoma ( ) Pancreatic tumour ( ) Polycythemia vera ( ) Relapsing-remitting multiple sclerosis ( ) Renal cell carcinoma ( ) Systemic sclerosis ( ) Type-1 diabetes ( ) Zika virus infection ( ) Dengue ( ) leukaemia ( ) Lupus ( ) Pancreatic cancer ( ) Asthma ( ) Chronic hepatitis B virus infection ( ) Leukemia ( ) Liver cancer ( )
UniProt ID	IFNA1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	3UX9
Pfam ID	PF00143
Sequence	MASPFALLMVLVVLSCKSSCSLGCDLPETHSLDNRRTLMLLAQMSRISPSSCLMDRHDFG FPQEEFDGNQFQKAPAISVLHELIQQIFNLFTTKDSSAAWDEDLLDKFCTELYQQLNDLE ACVMQEERVGETPLMNADSILAVKKYFRRITLYLTEKKYSPCAWEVVRAEIMRSLSLSTN LQERLRRKE
Function	Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.
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

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Tuberculosis	DIS2YIMD	Definitive	Altered Expression	[1]
Acquired immune deficiency syndrome	DISL5UOX	Strong	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Therapeutic	[4]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[5]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[6]
Anemia	DISTVL0C	Strong	Biomarker	[7]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[8]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[8]
Bacterial infection	DIS5QJ9S	Strong	Biomarker	[9]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[10]
Breast cancer	DIS7DPX1	Strong	Biomarker	[11]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[11]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Colorectal neoplasm	DISR1UCN	Strong	Therapeutic	[14]
Dermatomyositis	DIS50C5O	Strong	Altered Expression	[15]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[5]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[17]
Lung carcinoma	DISTR26C	Strong	Biomarker	[17]
Major depressive disorder	DIS4CL3X	Strong	Altered Expression	[18]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[19]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[20]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[21]
Pancreatic tumour	DIS3U0LK	Strong	Therapeutic	[4]
Polycythemia vera	DISB5FPO	Strong	Biomarker	[22]
Relapsing-remitting multiple sclerosis	DISSXFCF	Strong	Biomarker	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[12]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[24]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[25]
Zika virus infection	DISQUCTY	Strong	Biomarker	[26]
Dengue	DISKH221	moderate	Biomarker	[27]
leukaemia	DISS7D1V	moderate	Biomarker	[28]
Lupus	DISOKJWA	moderate	Biomarker	[29]
Pancreatic cancer	DISJC981	moderate	Biomarker	[30]
Asthma	DISW9QNS	Limited	Biomarker	[31]
Chronic hepatitis B virus infection	DISHL4NT	Limited	Biomarker	[32]
Leukemia	DISNAKFL	Limited	Biomarker	[28]
Liver cancer	DISDE4BI	Limited	Biomarker	[33]
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⏷ Show the Full List of 40 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Interferon alpha-1/13 (IFNA1) increases the response to substance of Doxorubicin.	[37]
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This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Interferon alpha-1/13 (IFNA1) increases the abundance of Fluorouracil.	[38]
PMID28870136-Compound-48	DMPIM9L	Patented	Interferon alpha-1/13 (IFNA1) decreases the metabolism of PMID28870136-Compound-48.	[39]
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3 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 alpha-1/13 (IFNA1).	[34]
Zidovudine	DM4KI7O	Approved	Zidovudine affects the expression of Interferon alpha-1/13 (IFNA1).	[2]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Interferon alpha-1/13 (IFNA1).	[36]
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References

1	HIV Infection Is Associated With Downregulation of BTLA Expression on Mycobacterium tuberculosis-Specific CD4 T Cells in Active Tuberculosis Disease.Front Immunol. 2019 Aug 21;10:1983. doi: 10.3389/fimmu.2019.01983. eCollection 2019.
2	Effect of zidovudine therapy in patients with HIV infection on endogenous interferon plasma levels and the hepatic cytochrome P450 enzyme system. Chemotherapy. 1998 May-Jun;44(3):174-80. doi: 10.1159/000007112.
3	Alpha-interferon improves survival and remission duration in P-190BCR-ABL positive adult acute lymphoblastic leukemia.Leukemia. 2000 Jan;14(1):22-7. doi: 10.1038/sj.leu.2401641.
4	Impact of interferon-alpha in combined chemoradioimmunotherapy for pancreatic adenocarcinoma (CapRI): first data from the immunomonitoring.J Immunother. 2007 Jan;30(1):108-15. doi: 10.1097/01.cji.0000211317.15278.27.
5	Human SLFN5 is a transcriptional co-repressor of STAT1-mediated interferon responses and promotes the malignant phenotype in glioblastoma.Oncogene. 2017 Oct 26;36(43):6006-6019. doi: 10.1038/onc.2017.205. Epub 2017 Jul 3.
6	A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients.Oncoimmunology. 2018 Feb 13;7(5):e1426423. doi: 10.1080/2162402X.2018.1426423. eCollection 2018.
7	Interferon-alpha Treatment for Disease Control in Metastatic Pheochromocytoma/Paraganglioma Patients.Horm Cancer. 2017 Dec;8(5-6):330-337. doi: 10.1007/s12672-017-0303-8. Epub 2017 Jul 26.
8	Signal Integration of IFN-I and IFN-II With TLR4 Involves Sequential Recruitment of STAT1-Complexes and NFB to Enhance Pro-inflammatory Transcription.Front Immunol. 2019 Jun 4;10:1253. doi: 10.3389/fimmu.2019.01253. eCollection 2019.
9	Mechanical Ventilation Impairs IL-17 Cytokine Family Expression in Ventilator-Associated Pneumonia.Int J Mol Sci. 2019 Oct 12;20(20):5072. doi: 10.3390/ijms20205072.
10	Enrichment pathway analysis. The inflammatory genetic background in Bipolar Disorder.J Affect Disord. 2015 Jul 1;179:88-94. doi: 10.1016/j.jad.2015.03.032. Epub 2015 Mar 26.
11	Progesterone Receptor Attenuates STAT1-Mediated IFN Signaling in Breast Cancer.J Immunol. 2019 May 15;202(10):3076-3086. doi: 10.4049/jimmunol.1801152. Epub 2019 Apr 1.
12	Nivolumab in the treatment of advanced renal cell carcinoma.Future Oncol. 2018 Jul;14(17):1679-1689. doi: 10.2217/fon-2017-0533. Epub 2018 Feb 20.
13	IFN/STAT signaling controls tumorigenesis and the drug response in colorectal cancer.Cancer Sci. 2019 Apr;110(4):1293-1305. doi: 10.1111/cas.13964. Epub 2019 Mar 22.
14	Anti-EpCAM monoclonal antibody (MAb17-1A) based treatment combined with alpha-interferon, 5-fluorouracil and granulocyte-macrophage colony-stimulating factor in patients with metastatic colorectal carcinoma.Int J Oncol. 2004 Sep;25(3):703-11.
15	Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti-melanoma differentiation-associated gene 5 dermatomyositis.Br J Dermatol. 2019 May;180(5):1090-1098. doi: 10.1111/bjd.16917. Epub 2018 Sep 26.
16	Murine Models of Hepatitis A Virus Infection.Cold Spring Harb Perspect Med. 2019 Jan 2;9(1):a031674. doi: 10.1101/cshperspect.a031674.
17	RNA-binding protein KHSRP promotes tumor growth and metastasis in non-small cell lung cancer.J Exp Clin Cancer Res. 2019 Nov 27;38(1):478. doi: 10.1186/s13046-019-1479-2.
18	Anhedonic-like behavior correlates with IFN serum levels in a two-hit model of depression.Behav Brain Res. 2019 Nov 5;373:112076. doi: 10.1016/j.bbr.2019.112076. Epub 2019 Jul 5.
19	Assessing the Metabolomic Profile of Multiple Sclerosis Patients Treated with Interferon Beta 1a by (1)H-NMR Spectroscopy.Neurotherapeutics. 2019 Jul;16(3):797-807. doi: 10.1007/s13311-019-00721-8.
20	Systemic exposure to a single dose of ferucarbotran aggravates neuroinflammation in a murine model of experimental autoimmune encephalomyelitis.Int J Nanomedicine. 2019 Feb 15;14:1229-1240. doi: 10.2147/IJN.S189327. eCollection 2019.
21	Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression.Oncoimmunology. 2017 Apr 28;6(6):e1320626. doi: 10.1080/2162402X.2017.1320626. eCollection 2017.
22	Alphaherpesvirus infection of mice primes PNS neurons to an inflammatory state regulated by TLR2 and type I IFN signaling.PLoS Pathog. 2019 Nov 1;15(11):e1008087. doi: 10.1371/journal.ppat.1008087. eCollection 2019 Nov.
23	Endogenous double-stranded Alu RNA elements stimulate IFN-responses in relapsing remitting multiple sclerosis.J Autoimmun. 2019 Jun;100:40-51. doi: 10.1016/j.jaut.2019.02.003. Epub 2019 Feb 28.
24	Innate immunity and interferons in the pathogenesis of Sjgren's syndrome.Rheumatology (Oxford). 2021 Jun 18;60(6):2561-2573. doi: 10.1093/rheumatology/key360.
25	Epigenetic modulation of cells by interferon- via PNPT1/mir-26a/TET2 triggers autoimmune diabetes.JCI Insight. 2019 Mar 7;4(5):e126663. doi: 10.1172/jci.insight.126663. eCollection 2019 Mar 7.
26	Protection of ZIKV infection-induced neuropathy by abrogation of acute antiviral response in human neural progenitors.Cell Death Differ. 2019 Dec;26(12):2607-2621. doi: 10.1038/s41418-019-0324-7. Epub 2019 Apr 5.
27	Characterization of a murine model of non-lethal, symptomatic dengue virus infection.Sci Rep. 2018 Mar 20;8(1):4900. doi: 10.1038/s41598-018-22618-w.
28	Twins with different personalities: STAT5B-but not STAT5A-has a key role in BCR/ABL-induced leukemia.Leukemia. 2019 Jul;33(7):1583-1597. doi: 10.1038/s41375-018-0369-5. Epub 2019 Jan 24.
29	Hypersensitive IFN Responses in Lupus Keratinocytes Reveal Key Mechanistic Determinants in Cutaneous Lupus.J Immunol. 2019 Apr 1;202(7):2121-2130. doi: 10.4049/jimmunol.1800650. Epub 2019 Feb 11.
30	Pancreatic adenocarcinoma upregulated factor (PAUF) confers resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNA receptor-mediated signaling.Biochem Biophys Res Commun. 2015 Apr 3;459(2):313-318. doi: 10.1016/j.bbrc.2015.02.107. Epub 2015 Feb 26.
31	Increased nuclear suppressor of cytokine signaling 1 in asthmatic bronchial epithelium suppresses rhinovirus induction of innate interferons.J Allergy Clin Immunol. 2015 Jul;136(1):177-188.e11. doi: 10.1016/j.jaci.2014.11.039. Epub 2015 Jan 25.
32	Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study.Clin Infect Dis. 2019 Nov 13;69(11):1969-1979. doi: 10.1093/cid/ciz084.
33	Vitamin K(2) supplementation blocks the beneficial effects of IFN--2b administered on the early stages of liver cancer development in rats.Nutrition. 2019 Mar;59:170-179. doi: 10.1016/j.nut.2018.08.016. Epub 2018 Aug 25.
34	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.
35	Effect of zidovudine therapy in patients with HIV infection on endogenous interferon plasma levels and the hepatic cytochrome P450 enzyme system. Chemotherapy. 1998 May-Jun;44(3):174-80. doi: 10.1159/000007112.
36	Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
37	Interferon-alpha enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis. Acta Pharmacol Sin. 2007 Nov;28(11):1835-41. doi: 10.1111/j.1745-7254.2007.00662.x.
38	Influence of chemotherapeutic agents and cytokines on the expression of 5-fluorouracil-associated enzymes in human colon cancer cell lines. J Gastroenterol. 2006 Feb;41(2):140-50.
39	Effects of interferon-alpha monotherapy on hepatic drug metabolism in cancer patients. Br J Clin Pharmacol. 1993 Sep;36(3):229-35. doi: 10.1111/j.1365-2125.1993.tb04222.x.