Drug Information

Drug (ID: DG00436) and It's Reported Resistant Information
Name
IFN-alpha
Synonyms
IFN alpha-IFNAR-IN-1; 844882-93-5; IFN-alpha; CHEMBL1617534; DNDI1417107; N-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine; Methyl-[2-(naphthalen-1-ylsulfanyl)-benzyl]-amine; IFNAR-IN-1; ZINC346644; BDBM50014088; AKOS005066179; HY-12836; N-Methyl-2-(1-naphthylthio)benzenemethaneamine; A915034; N-methyl-1-(2-(naphthalen-1-ylthio)phenyl)methanamine; BENZENEMETHANAMINE,N-METHYL-2-(1-NAPHTHALENYLTHIO)-
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Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Liver cancer [ICD-11: 2C12]
[1]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Liver cancer [ICD-11: 2C12]
[2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C18H17NS
IsoSMILES
CNCC1=CC=CC=C1SC2=CC=CC3=CC=CC=C32
InChI
1S/C18H17NS/c1-19-13-15-8-3-5-11-17(15)20-18-12-6-9-14-7-2-4-10-16(14)18/h2-12,19H,13H2,1H3
InChIKey
OHDXDNUPVVYWOV-UHFFFAOYSA-N
PubChem CID
826634
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Liver cancer [ICD-11: 2C12]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-146a [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Wnt/Beta signaling pathway Activation hsa04310
In Vitro Model PLC/PRF/5 cells Liver Homo sapiens (Human) CVCL_0485
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-146a confers resistance to IFN-alpha in HCC cells by inhibiting apoptosis through SMAD4.
Key Molecule: hsa-mir-21 [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
PLC/PRF/5 cells Liver Homo sapiens (Human) CVCL_0485
HLE cells Liver Homo sapiens (Human) CVCL_1281
HLF cells Liver Homo sapiens (Human) CVCL_2947
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Hepatocellular carcinoma cells transfected with pre-miR-21 were significantly resistant to IFN-alpha/5-FU. Transfection of anti-miR-21 rendered HCC cells sensitive to IFN-alpha/5-FU, and such sensitivity was weakened by transfection of siRNAs of target molecules, PETN and PDCD4, miR-21 induces chemoresistance to IFN-alpha and 5-FU, mediated through PETN and PDCD4.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Mothers against decapentaplegic homolog 4 (SMAD4) [2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Wnt/Beta signaling pathway Activation hsa04310
In Vitro Model PLC/PRF/5 cells Liver Homo sapiens (Human) CVCL_0485
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-146a confers resistance to IFN-alpha in HCC cells by inhibiting apoptosis through SMAD4.
Key Molecule: Programmed cell death protein 4 (PDCD4) [1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
PLC/PRF/5 cells Liver Homo sapiens (Human) CVCL_0485
HLE cells Liver Homo sapiens (Human) CVCL_1281
HLF cells Liver Homo sapiens (Human) CVCL_2947
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Hepatocellular carcinoma cells transfected with pre-miR-21 were significantly resistant to IFN-alpha/5-FU. Transfection of anti-miR-21 rendered HCC cells sensitive to IFN-alpha/5-FU, and such sensitivity was weakened by transfection of siRNAs of target molecules, PETN and PDCD4, miR-21 induces chemoresistance to IFN-alpha and 5-FU, mediated through PETN and PDCD4.
Key Molecule: Phosphatase and tensin homolog (PTEN) [1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell viability Activation hsa05200
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
PLC/PRF/5 cells Liver Homo sapiens (Human) CVCL_0485
HLE cells Liver Homo sapiens (Human) CVCL_1281
HLF cells Liver Homo sapiens (Human) CVCL_2947
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Hepatocellular carcinoma cells transfected with pre-miR-21 were significantly resistant to IFN-alpha/5-FU. Transfection of anti-miR-21 rendered HCC cells sensitive to IFN-alpha/5-FU, and such sensitivity was weakened by transfection of siRNAs of target molecules, PETN and PDCD4, miR-21 induces chemoresistance to IFN-alpha and 5-FU, mediated through PETN and PDCD4.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Long non-protein coding RNA 607 (LINC00607) [3]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
NF-kappaB p65/p53 signaling pathway Regulation hsa04064
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
HCCLM3 cells Liver Homo sapiens (Human) CVCL_6832
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
MHCC97-H cells Liver Homo sapiens (Human) CVCL_4972
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Real-time RT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description LncRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity, inhibiting the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Cellular tumor antigen p53 (TP53) [3]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
NF-kappaB p65/p53 signaling pathway Regulation hsa04064
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
HCCLM3 cells Liver Homo sapiens (Human) CVCL_6832
Hep3B cells Liver Homo sapiens (Human) CVCL_0326
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
PLC cells Liver Homo sapiens (Human) CVCL_0485
MHCC97-H cells Liver Homo sapiens (Human) CVCL_4972
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description LncRNA 00607 overexpression leads to decreased HCC cell proliferation in vitro and in vivo, enhanced apoptosis and chemotherapeutic drug sensitivity, inhibiting the p65 transcription by binding to the p65 promoter region, therefore contributing to increased p53 levels in HCC.
References
Ref 1 MicroRNA-21 induces resistance to the anti-tumour effect of interferon-Alpha/5-fluorouracil in hepatocellular carcinoma cells. Br J Cancer. 2010 Nov 9;103(10):1617-26. doi: 10.1038/sj.bjc.6605958. Epub 2010 Oct 26.
Ref 2 miR-146a suppresses the sensitivity to interferon-Alpha in hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2011 Nov 4;414(4):675-80. doi: 10.1016/j.bbrc.2011.09.124. Epub 2011 Oct 1.
Ref 3 Long non-coding RNA 00607 as a tumor suppressor by modulating NF-kB p65/p53 signaling axis in hepatocellular carcinoma. Carcinogenesis. 2018 Dec 31;39(12):1438-1446. doi: 10.1093/carcin/bgy113.

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