Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSR2UBI)

• DOT Name: Serpin B3 (SERPINB3)
• Synonyms: Protein T4-A; Squamous cell carcinoma antigen 1; SCCA-1
• Gene Name: SERPINB3
• UniProt ID: SPB3_HUMAN
• PDB ID: 2ZV6; 4ZK0; 4ZK3
• Pfam ID: PF00079
• Sequence:
  MNSLSEANTKFMFDLFQQFRKSKENNIFYSPISITSALGMVLLGAKDNTAQQIKKVLHFD
  QVTENTTGKAATYHVDRSGNVHHQFQKLLTEFNKSTDAYELKIANKLFGEKTYLFLQEYL
  DAIKKFYQTSVESVDFANAPEESRKKINSWVESQTNEKIKNLIPEGNIGSNTTLVLVNAI
  YFKGQWEKKFNKEDTKEEKFWPNKNTYKSIQMMRQYTSFHFASLEDVQAKVLEIPYKGKD
  LSMIVLLPNEIDGLQKLEEKLTAEKLMEWTSLQNMRETRVDLHLPRFKVEESYDLKDTLR
  TMGMVDIFNGDADLSGMTGSRGLVLSGVLHKAFVEVTEEGAEAAAATAVVGFGSSPTSTN
  EEFHCNHPFLFFIRQNKTNSILFYGRFSSP
• Function: May act as a papain-like cysteine protease inhibitor to modulate the host immune response against tumor cells. Also functions as an inhibitor of UV-induced apoptosis via suppression of the activity of c-Jun NH(2)-terminal kinase (JNK1).
• Tissue Specificity: Squamous cells. Expressed in some hepatocellular carcinoma (at protein level).
• KEGG Pathway: Amoebiasis (hsa05146)
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

13 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 B3 (SERPINB3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serpin B3 (SERPINB3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serpin B3 (SERPINB3).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Serpin B3 (SERPINB3).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Serpin B3 (SERPINB3).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Serpin B3 (SERPINB3).	[6]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Serpin B3 (SERPINB3).	[7]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Serpin B3 (SERPINB3).	[5]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Serpin B3 (SERPINB3).	[7]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Serpin B3 (SERPINB3).	[7]
Resorcinol	DMM37C0	Investigative	Resorcinol increases the expression of Serpin B3 (SERPINB3).	[7]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Serpin B3 (SERPINB3).	[7]
Farnesol	DMV2X1B	Investigative	Farnesol increases the expression of Serpin B3 (SERPINB3).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Serpin B3 (SERPINB3).	[8]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Deguelin	DMXT7WG	Investigative	Deguelin decreases the secretion of Serpin B3 (SERPINB3).	[9]

References

• [1] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [2] Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
• [3] 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.
• [4] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [5] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] The THP-1 cell toolbox: a new concept integrating the key events of skin sensitization. Arch Toxicol. 2019 Apr;93(4):941-951.
• [8] 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.
• [9] Deguelin inhibits the migration and invasion of lung cancer A549 and H460 cells via regulating actin cytoskeleton rearrangement. Int J Clin Exp Pathol. 2015 Dec 1;8(12):15582-90. eCollection 2015.