Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT88LHZ8)

DOT Name Serpin B4 (SERPINB4)
Synonyms Leupin; Peptidase inhibitor 11; PI-11; Squamous cell carcinoma antigen 2; SCCA-2
Gene Name SERPINB4
Related Disease
Asthma ( )
Lung adenocarcinoma ( )
Adult hepatocellular carcinoma ( )
Atopic dermatitis ( )
Carcinoma of esophagus ( )
Cervical cancer ( )
Cervical carcinoma ( )
Cutaneous squamous cell carcinoma ( )
Esophageal adenocarcinoma ( )
Esophageal cancer ( )
Exanthem ( )
Familial multiple trichoepithelioma ( )
Head-neck squamous cell carcinoma ( )
Hepatitis ( )
Hepatitis A virus infection ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Lichen planus ( )
Liver cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm of esophagus ( )
Non-small-cell lung cancer ( )
Psoriasis ( )
Skin cancer ( )
Skin neoplasm ( )
Neoplasm ( )
Adenocarcinoma ( )
Advanced cancer ( )
Alcoholic cirrhosis of liver ( )
Contact dermatitis ( )
Melanoma ( )
Squamous cell carcinoma ( )
UniProt ID
SPB4_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00079
Sequence
MNSLSEANTKFMFDLFQQFRKSKENNIFYSPISITSALGMVLLGAKDNTAQQISKVLHFD
QVTENTTEKAATYHVDRSGNVHHQFQKLLTEFNKSTDAYELKIANKLFGEKTYQFLQEYL
DAIKKFYQTSVESTDFANAPEESRKKINSWVESQTNEKIKNLFPDGTIGNDTTLVLVNAI
YFKGQWENKFKKENTKEEKFWPNKNTYKSVQMMRQYNSFNFALLEDVQAKVLEIPYKGKD
LSMIVLLPNEIDGLQKLEEKLTAEKLMEWTSLQNMRETCVDLHLPRFKMEESYDLKDTLR
TMGMVNIFNGDADLSGMTWSHGLSVSKVLHKAFVEVTEEGVEAAAATAVVVVELSSPSTN
EEFCCNHPFLFFIRQNKTNSILFYGRFSSP
Function May act as a protease inhibitor to modulate the host immune response against tumor cells.
Tissue Specificity Squamous cells.
KEGG Pathway
Amoebiasis (hsa05146 )

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Asthma DISW9QNS Definitive Biomarker [1]
Lung adenocarcinoma DISD51WR Definitive Biomarker [2]
Adult hepatocellular carcinoma DIS6ZPAI Strong Biomarker [3]
Atopic dermatitis DISTCP41 Strong Biomarker [4]
Carcinoma of esophagus DISS6G4D Strong Biomarker [5]
Cervical cancer DISFSHPF Strong Biomarker [6]
Cervical carcinoma DIST4S00 Strong Biomarker [6]
Cutaneous squamous cell carcinoma DIS3LXUG Strong Altered Expression [7]
Esophageal adenocarcinoma DISODWFP Strong Biomarker [5]
Esophageal cancer DISGB2VN Strong Biomarker [5]
Exanthem DISAFOQN Strong Altered Expression [8]
Familial multiple trichoepithelioma DISKZAUY Strong Altered Expression [5]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [9]
Hepatitis DISXXX35 Strong Altered Expression [10]
Hepatitis A virus infection DISUMFQV Strong Altered Expression [10]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [10]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [11]
Lichen planus DISRPMMS Strong Altered Expression [12]
Liver cancer DISDE4BI Strong Biomarker [3]
Lung cancer DISCM4YA Strong Biomarker [13]
Lung carcinoma DISTR26C Strong Biomarker [13]
Neoplasm of esophagus DISOLKAQ Strong Biomarker [5]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [14]
Psoriasis DIS59VMN Strong Biomarker [1]
Skin cancer DISTM18U Strong Genetic Variation [7]
Skin neoplasm DIS16DDV Strong Genetic Variation [7]
Neoplasm DISZKGEW moderate Biomarker [5]
Adenocarcinoma DIS3IHTY Limited Altered Expression [14]
Advanced cancer DISAT1Z9 Limited Altered Expression [15]
Alcoholic cirrhosis of liver DISQ1WRT Limited Biomarker [16]
Contact dermatitis DISQ3AU0 Limited Biomarker [17]
Melanoma DIS1RRCY Limited Genetic Variation [18]
Squamous cell carcinoma DISQVIFL Limited Biomarker [1]
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⏷ Show the Full List of 33 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Serpin B4 (SERPINB4). [19]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Serpin B4 (SERPINB4). [20]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Serpin B4 (SERPINB4). [21]
Methotrexate DM2TEOL Approved Methotrexate increases the expression of Serpin B4 (SERPINB4). [22]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Serpin B4 (SERPINB4). [21]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of Serpin B4 (SERPINB4). [23]
Amphotericin B DMTAJQE Approved Amphotericin B decreases the expression of Serpin B4 (SERPINB4). [24]
Benzatropine DMF7EXL Approved Benzatropine increases the expression of Serpin B4 (SERPINB4). [23]
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⏷ Show the Full List of 8 Drug(s)

References

1 Squamous Cell Carcinoma Antigen 2 (SCCA2, SERPINB4): An Emerging Biomarker for Skin Inflammatory Diseases.Int J Mol Sci. 2018 Apr 6;19(4):1102. doi: 10.3390/ijms19041102.
2 Transcriptional targeting of adenovirus vectors with the squamous cell carcinoma-specific antigen-2 promoter for selective apoptosis induction in lung cancer.Cancer Gene Ther. 2006 Sep;13(9):856-63. doi: 10.1038/sj.cgt.7700953. Epub 2006 May 19.
3 AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease.BMC Cancer. 2008 Jul 18;8:200. doi: 10.1186/1471-2407-8-200.
4 Serum squamous cell carcinoma antigen (SCCA)-2 correlates with clinical severity of pediatric atopic dermatitis in Ishigaki cohort.J Dermatol Sci. 2019 Aug;95(2):70-75. doi: 10.1016/j.jdermsci.2019.07.005. Epub 2019 Jul 24.
5 Squamous cell carcinoma antigen 1 is associated to poor prognosis in esophageal cancer through immune surveillance impairment and reduced chemosensitivity.Cancer Sci. 2019 May;110(5):1552-1563. doi: 10.1111/cas.13986. Epub 2019 Apr 15.
6 Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer.Br J Cancer. 2018 Jan;118(1):72-78. doi: 10.1038/bjc.2017.390. Epub 2017 Nov 7.
7 SCCA2-like serpins mediate genetic predisposition to skin tumors.Cancer Res. 2003 Apr 15;63(8):1871-5.
8 Serum levels of squamous cell carcinoma antigens 1 and 2 reflect disease severity and clinical type of atopic dermatitis in adult patients.Allergol Int. 2018 Jan;67(1):124-130. doi: 10.1016/j.alit.2017.06.016. Epub 2017 Jul 19.
9 Technical and clinical performance of a new assay to detect squamous cell carcinoma antigen levels for the differential diagnosis of cervical, lung, and head and neck cancer.Tumour Biol. 2018 Apr;40(4):1010428318772202. doi: 10.1177/1010428318772202.
10 Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus.Int J Nanomedicine. 2012;7:827-34. doi: 10.2147/IJN.S27803. Epub 2012 Feb 16.
11 Squamous cell carcinoma antigen-1 (SERPINB3) polymorphism in chronic liver disease.Dig Liver Dis. 2009 Mar;41(3):212-6. doi: 10.1016/j.dld.2008.06.001. Epub 2008 Jul 25.
12 Measurement of squamous cell carcinoma antigen 2 in lichen planus patients.J Cosmet Dermatol. 2020 Jul;19(7):1780-1784. doi: 10.1111/jocd.13216. Epub 2019 Dec 9.
13 Squamous cell carcinoma antigen 1 promotes caspase-8-mediated apoptosis in response to endoplasmic reticulum stress while inhibiting necrosis induced by lysosomal injury.Mol Cell Biol. 2011 Jul;31(14):2902-19. doi: 10.1128/MCB.05452-11. Epub 2011 May 16.
14 Maspin - the most commonly-expressed gene of the 18q21.3 serpin cluster in lung cancer - is strongly expressed in preneoplastic bronchial lesions.Oncogene. 2003 Nov 27;22(54):8677-87. doi: 10.1038/sj.onc.1207127.
15 The clinical value of serum squamous cell carcinoma antigens 1 and 2 in head and neck squamous cell carcinoma.Auris Nasus Larynx. 2019 Feb;46(1):135-140. doi: 10.1016/j.anl.2018.07.010. Epub 2018 Aug 2.
16 Diagnostic specificity and sensitivity of PIVKAII, GP3, CSTB, SCCA1 and HGF for the diagnosis of hepatocellular carcinoma in patients with alcoholic liver cirrhosis.Ann Clin Biochem. 2018 May;55(3):355-362. doi: 10.1177/0004563217726808. Epub 2017 Sep 20.
17 Genes specifically modulated in sensitized skins allow the detection of sensitizers in a reconstructed human skin modelDevelopment of the SENS-IS assay. Toxicol In Vitro. 2015 Jun;29(4):787-802.
18 Recurrent SERPINB3 and SERPINB4 mutations in patients who respond to anti-CTLA4 immunotherapy.Nat Genet. 2016 Nov;48(11):1327-1329. doi: 10.1038/ng.3677. Epub 2016 Sep 26.
19 Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
20 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
21 Analysis of the in vitro synergistic effect of 5-fluorouracil and cisplatin on cervical carcinoma cells. Int J Gynecol Cancer. 2006 May-Jun;16(3):1321-9.
22 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
23 Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
24 Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.