Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ95LR2)

• DOT Name: Serpin B7 (SERPINB7)
• Synonyms: Megsin; TP55
• Gene Name: SERPINB7
• Related Disease:
  Matthew-Wood syndrome
  Nephritis
  Palmoplantar keratoderma, Nagashima type
  Palmoplantar keratosis
  Asthma
• UniProt ID: SPB7_HUMAN
• Pfam ID: PF00079
• Sequence:
  MASLAAANAEFCFNLFREMDDNQGNGNVFFSSLSLFAALALVRLGAQDDSLSQIDKLLHV
  NTASGYGNSSNSQSGLQSQLKRVFSDINASHKDYDLSIVNGLFAEKVYGFHKDYIECAEK
  LYDAKVERVDFTNHLEDTRRNINKWVENETHGKIKNVIGEGGISSSAVMVLVNAVYFKGK
  WQSAFTKSETINCHFKSPKCSGKAVAMMHQERKFNLSVIEDPSMKILELRYNGGINMYVL
  LPENDLSEIENKLTFQNLMEWTNPRRMTSKYVEVFFPQFKIEKNYEMKQYLRALGLKDIF
  DESKADLSGIASGGRLYISRMMHKSYIEVTEEGTEATAATGSNIVEKQLPQSTLFRADHP
  FLFVIRKDDIILFSGKVSCP
• Function: Might function as an inhibitor of Lys-specific proteases. Might influence the maturation of megakaryocytes via its action as a serpin.
• Tissue Specificity: Predominantly expressed in mesangial cells. Expressed in the epidermis of the whole body.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[1]
Nephritis	DISQZQ70	Strong	Biomarker	[2]
Palmoplantar keratoderma, Nagashima type	DISDW4KK	Strong	Autosomal recessive	[3]
Palmoplantar keratosis	DISYQGFB	moderate	Genetic Variation	[4]
Asthma	DISW9QNS	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serpin B7 (SERPINB7).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Serpin B7 (SERPINB7).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Serpin B7 (SERPINB7).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Serpin B7 (SERPINB7).	[9]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Serpin B7 (SERPINB7).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Serpin B7 (SERPINB7).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serpin B7 (SERPINB7).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serpin B7 (SERPINB7).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Serpin B7 (SERPINB7).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Serpin B7 (SERPINB7).	[12]

References

• [1] SERPINB7 Expression Predicts Poor Pancreatic Cancer Survival Upon Gemcitabine Treatment.Transl Oncol. 2019 Jan;12(1):15-23. doi: 10.1016/j.tranon.2018.08.019. Epub 2018 Sep 20.
• [2] Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis.Kidney Int. 2001 Aug;60(2):641-52. doi: 10.1046/j.1523-1755.2001.060002641.x.
• [3] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [4] Nagashima-type palmoplantar keratosis in Finland caused by a SERPINB7 founder mutation.J Am Acad Dermatol. 2020 Aug;83(2):643-645. doi: 10.1016/j.jaad.2019.11.004. Epub 2019 Nov 7.
• [5] Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.Am J Hum Genet. 2019 Apr 4;104(4):665-684. doi: 10.1016/j.ajhg.2019.02.022. Epub 2019 Mar 28.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] 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.
• [11] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.