Target Information
| Target General Information | Top | |||||
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| Target ID |
T63934
(Former ID: TTDI01921)
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| Target Name |
Interferon-alpha 2 (IFNA2)
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| Synonyms |
LeIF A; Interferon alphaA; Interferon alpha2; Interferon alpha-A; Interferon alpha-2; IFNalpha2; IFNA2C; IFNA2B; IFNA2A; IFN-alpha-2
Click to Show/Hide
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| Gene Name |
IFNA2
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
| 2 | Mature B-cell leukaemia [ICD-11: 2A82] | |||||
| 3 | Melanoma [ICD-11: 2C30] | |||||
| Function |
Produced by macrophages, IFN-alpha have antiviral activities.
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| BioChemical Class |
Cytokine: interferon
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| UniProt ID | ||||||
| Sequence |
MALTFALLVALLVLSCKSSCSVGCDLPQTHSLGSRRTLMLLAQMRKISLFSCLKDRHDFG
FPQEEFGNQFQKAETIPVLHEMIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEA CVIQGVGVTETPLMKEDSILAVRKYFQRITLYLKEKKYSPCAWEVVRAEIMRSFSLSTNL QESLRSKE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Interferon Alfa-2b | Drug Info | Approved | Melanoma | [2] | |
| 2 | Peginterferon alfa-2a | Drug Info | Approved | Hairy cell leukaemia | [3] | |
| 3 | Peginterferon alfa-2b | Drug Info | Approved | Hepatitis C virus infection | [3], [4] | |
| Clinical Trial Drug(s) | [+] 9 Clinical Trial Drugs | + | ||||
| 1 | Albinterferon alfa-2b | Drug Info | Phase 3 | Hepatitis C virus infection | [5] | |
| 2 | Hebergel | Drug Info | Phase 3 | Virus infection | [6] | |
| 3 | Interferon alpha 2a | Drug Info | Phase 3 | Hepatitis C virus infection | [7] | |
| 4 | P-1101 | Drug Info | Phase 3 | Hepatitis B virus infection | [8] | |
| 5 | Instiladrin | Drug Info | Phase 2 | Bladder cancer | [9] | |
| 6 | Interferon alpha-2b | Drug Info | Phase 2 | Hepatitis C virus infection | [10] | |
| 7 | Novaferon | Drug Info | Phase 2 | Colorectal cancer | [11] | |
| 8 | CIGB-128 | Drug Info | Phase 1 | Basal cell carcinoma | [12] | |
| 9 | SCH-721015 | Drug Info | Phase 1 | Mesothelioma | [13] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 14 Modulator drugs | + | ||||
| 1 | Interferon Alfa-2b | Drug Info | [1] | |||
| 2 | Peginterferon alfa-2a | Drug Info | [1] | |||
| 3 | Peginterferon alfa-2b | Drug Info | [1] | |||
| 4 | Albinterferon alfa-2b | Drug Info | [5] | |||
| 5 | Hebergel | Drug Info | [14] | |||
| 6 | Interferon alpha 2a | Drug Info | [15] | |||
| 7 | P-1101 | Drug Info | [16] | |||
| 8 | Instiladrin | Drug Info | [9] | |||
| 9 | Interferon alpha-2b | Drug Info | [17] | |||
| 10 | Novaferon | Drug Info | [18] | |||
| 11 | CIGB-128 | Drug Info | [19] | |||
| 12 | SCH-721015 | Drug Info | [20] | |||
| 13 | HAp-IFN | Drug Info | [21] | |||
| 14 | subalin | Drug Info | [22] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: N-Acetyl-2-deoxy-2-amino-galactose | Ligand Info | |||||
| Structure Description | A single GalNAc residue on Threonine-106 modifies the dynamics and the structure of Interferon alpha-2a around the glycosylation site | PDB:2LMS | ||||
| Method | Solution NMR | Resolution | N.A. | Mutation | No | [23] |
| PDB Sequence |
CDLPQTHSLG
10 SRRTLMLLAQ20 MRKISLFSCL30 KDRHDFGFPQ40 EEFGNQFQKA50 ETIPVLHEMI 60 QQIFNLFSTK70 DSSAAWDETL80 LDKFYTELYQ90 QLNDLEACVI100 QGVGVTETPL 110 MKEDSILAVR120 KYFQRITLYL130 KEKKYSPCAW140 EVVRAEIMRS150 FSLSTNLQES 160 LRSKE
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Necroptosis | hsa04217 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Toll-like receptor signaling pathway | hsa04620 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| NOD-like receptor signaling pathway | hsa04621 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| RIG-I-like receptor signaling pathway | hsa04622 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Cytosolic DNA-sensing pathway | hsa04623 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| JAK-STAT signaling pathway | hsa04630 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Natural killer cell mediated cytotoxicity | hsa04650 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 1.50E-06 |
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| Closeness centrality | 2.02E-01 | Radiality | 1.35E+01 | Clustering coefficient | 3.33E-01 |
| Neighborhood connectivity | 2.95E+01 | Topological coefficient | 4.04E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| References | Top | |||||
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| REF 1 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 4 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7462). | |||||
| REF 5 | Albinterferon alfa-2b, a novel fusion protein of human albumin and human interferon alfa-2b, for chronic hepatitis C. Curr Med Res Opin. 2009 Apr;25(4):991-1002. | |||||
| REF 6 | Detection of PEGylated proteins in polyacrylamide gels by reverse staining with zinc and imidazole salts. Electrophoresis. 2008 Jun;29(11):2363-71. | |||||
| REF 7 | Phase III trial of interferon alfa-2a with or without 13-cis-retinoic acid for patients with advanced renal cell carcinoma. J Clin Oncol. 2000 Aug;18(16):2972-80. | |||||
| REF 8 | ClinicalTrials.gov (NCT01949805) Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT01687244) Intravesical Administration of rAd-IFN/Syn3 in Patients With BCG-Refractory or Relapsed Bladder Cancer. U.S. National Institutes of Health. | |||||
| REF 10 | Clinical pipeline report, company report or official report of Hanall biopharma. | |||||
| REF 11 | ClinicalTrials.gov (NCT02455596) Recombinant Anti-tumor and Anti-virus Protein for Injection to Treat Advanced Neuroendocrine Tumors. | |||||
| REF 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037683) | |||||
| REF 13 | ClinicalTrials.gov (NCT01162785) Phase IB Intravesical Administration of SCH 721015. U.S. National Institutes of Health. | |||||
| REF 14 | Evaluation of recombinant human interferon alpha-2b structure and stability by in-gel tryptic digestion, H/D exchange and mass spectrometry. J Pharm Biomed Anal. 2006 Feb 24;40(3):781-7. | |||||
| REF 15 | Hairy cell leukemia associated with large granular lymphocyte leukemia: immunologic and genomic study, effect of interferon treatment. Blood. 1988 Aug;72(2):655-60. | |||||
| REF 16 | Effects of PEG-interferon-alpha-2A on Schistosoma mansoni infection in mice. J Parasitol. 2010 Aug;96(4):703-8. | |||||
| REF 17 | Clinical pipeline report, company report or official report of Avarx. | |||||
| REF 18 | Novaferon, a novel recombinant protein produced by DNA-shuffling of IFN-alpha, shows antitumor effect in vitro and in vivo. Cancer Cell Int. 2014; 14: 8. | |||||
| REF 19 | Pharmacokinetic and pharmacodynamic characterization of a new formulation containing synergistic proportions of interferons alpha-2b and gamma (HeberPAG) in patients with mycosis fungoides: an open-label trial.BMC Pharmacol Toxicol.2012 Dec 28;13:20. | |||||
| REF 20 | Toxicity and exposure of an adenovirus containing human interferon alpha-2b following intracystic administration in cynomolgus monkeys. Gene Ther. 2012 Jul;19(7):742-51. | |||||
| REF 21 | CN patent application no. 1921880, Protein drug sustained-release microparticle preparation for injection and process for producing the same. | |||||
| REF 22 | [Adjuvant properties of subalin, a recombinant interferon-producing probiotic].Zh Mikrobiol Epidemiol Immunobiol.2001 Nov-Dec;(6):77-82. | |||||
| REF 23 | A single N-acetylgalactosamine residue at threonine 106 modifies the dynamics and structure of interferon Alpha2a around the glycosylation site. J Biol Chem. 2013 Jan 4;288(1):247-54. | |||||
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