Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5T4Y5R)

• DOT Name: Serpin B8 (SERPINB8)
• Synonyms: Cytoplasmic antiproteinase 2; CAP-2; CAP2; Peptidase inhibitor 8; PI-8
• Gene Name: SERPINB8
• Related Disease:
  Palmoplantar pustulosis
  Peeling skin syndrome 5
  Psoriasis
  Age-related macular degeneration
  Exfoliative ichthyosis
• UniProt ID: SPB8_HUMAN
• Pfam ID: PF00079
• Sequence:
  MDDLCEANGTFAISLFKILGEEDNSRNVFFSPMSISSALAMVFMGAKGSTAAQMSQALCL
  YKDGDIHRGFQSLLSEVNRTGTQYLLRTANRLFGEKTCDFLPDFKEYCQKFYQAELEELS
  FAEDTEECRKHINDWVAEKTEGKISEVLDAGTVDPLTKLVLVNAIYFKGKWNEQFDRKYT
  RGMLFKTNEEKKTVQMMFKEAKFKMGYADEVHTQVLELPYVEEELSMVILLPDDNTDLAV
  VEKALTYEKFKAWTNSEKLTKSKVQVFLPRLKLEESYDLEPFLRRLGMIDAFDEAKADFS
  GMSTEKNVPLSKVAHKCFVEVNEEGTEAAAATAVVRNSRCSRMEPRFCADHPFLFFIRHH
  KTNCILFCGRFSSP
• Function: Has an important role in epithelial desmosome-mediated cell-cell adhesion.
• Reactome Pathway: Dissolution of Fibrin Clot (R-HSA-75205)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Palmoplantar pustulosis	DISCNSWD	Strong	Biomarker	[1]
Peeling skin syndrome 5	DIS1UGC5	Strong	Autosomal recessive	[2]
Psoriasis	DIS59VMN	Strong	Biomarker	[1]
Age-related macular degeneration	DIS0XS2C	moderate	Genetic Variation	[3]
Exfoliative ichthyosis	DISH776B	Supportive	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Serpin B8 (SERPINB8).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serpin B8 (SERPINB8).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serpin B8 (SERPINB8).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serpin B8 (SERPINB8).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serpin B8 (SERPINB8).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serpin B8 (SERPINB8).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serpin B8 (SERPINB8).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serpin B8 (SERPINB8).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serpin B8 (SERPINB8).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serpin B8 (SERPINB8).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Serpin B8 (SERPINB8).	[14]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Serpin B8 (SERPINB8).	[15]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Serpin B8 (SERPINB8).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Serpin B8 (SERPINB8).	[7]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Serpin B8 (SERPINB8).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serpin B8 (SERPINB8).	[17]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Serpin B8 (SERPINB8).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serpin B8 (SERPINB8).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Serpin B8 (SERPINB8).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Serpin B8 (SERPINB8).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serpin B8 (SERPINB8).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serpin B8 (SERPINB8).	[22]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Serpin B8 (SERPINB8).	[23]

References

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• [3] Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.Ann Hum Genet. 2013 May;77(3):215-31. doi: 10.1111/ahg.12011.
• [4] Loss-of-Function Mutations in SERPINB8 Linked to Exfoliative Ichthyosis with Impaired Mechanical Stability of Intercellular Adhesions. Am J Hum Genet. 2016 Aug 4;99(2):430-6. doi: 10.1016/j.ajhg.2016.06.004. Epub 2016 Jul 28.
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• [7] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
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• [11] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [15] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [19] Inter- and intra-laboratory study to determine the reproducibility of toxicogenomics datasets. Toxicology. 2011 Nov 28;290(1):50-8.
• [20] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [21] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.