Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5ZM0X6)

• DOT Name: Serpin B10 (SERPINB10)
• Synonyms: Bomapin; Peptidase inhibitor 10; PI-10
• Gene Name: SERPINB10
• Related Disease:
  Asthma
  Prostate cancer
  Prostate neoplasm
• UniProt ID: SPB10_HUMAN
• Pfam ID: PF00079
• Sequence:
  MDSLATSINQFALELSKKLAESAQGKNIFFSSWSISTSLTIVYLGAKGTTAAQMAQVLQF
  NRDQGVKCDPESEKKRKMEFNLSNSEEIHSDFQTLISEILKPNDDYLLKTANAIYGEKTY
  AFHNKYLEDMKTYFGAEPQPVNFVEASDQIRKDINSWVERQTEGKIQNLLPDDSVDSTTR
  MILVNALYFKGIWEHQFLVQNTTEKPFRINETTSKPVQMMFMKKKLHIFHIEKPKAVGLQ
  LYYKSRDLSLLILLPEDINGLEQLEKAITYEKLNEWTSADMMELYEVQLHLPKFKLEDSY
  DLKSTLSSMGMSDAFSQSKADFSGMSSARNLFLSNVFHKAFVEINEQGTEAAAGSGSEID
  IRIRVPSIEFNANHPFLFFIRHNKTNTILFYGRLCSP
• Function: Protease inhibitor that may play a role in the regulation of protease activities during hematopoiesis and apoptosis induced by TNF. May regulate protease activities in the cytoplasm and in the nucleus.
• Tissue Specificity: Expressed specifically in myeloid cells and the bone marrow.
• KEGG Pathway: Amoebiasis (hsa05146)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Altered Expression	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serpin B10 (SERPINB10).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Serpin B10 (SERPINB10).	[4]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Serpin B10 (SERPINB10).	[5]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Serpin B10 (SERPINB10).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serpin B10 (SERPINB10).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serpin B10 (SERPINB10).	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Serpin B10 (SERPINB10).	[7]

References

• [1] Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation.Am J Physiol Lung Cell Mol Physiol. 2019 Jan 1;316(1):L245-L254. doi: 10.1152/ajplung.00362.2017. Epub 2018 Nov 1.
• [2] Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer.J Hum Genet. 2005;50(10):507-515. doi: 10.1007/s10038-005-0285-1. Epub 2005 Sep 20.
• [3] 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.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [6] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.