Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6O7Y14)

• DOT Name: S100P-binding protein (S100PBP)
• Synonyms: S100P-binding protein Riken
• Gene Name: S100PBP
• Related Disease:
  Matthew-Wood syndrome
  Advanced cancer
  Pancreatic cancer
  Adenocarcinoma
• UniProt ID: S1PBP_HUMAN
• Pfam ID: PF15427
• Sequence:
  MMCSRVPSEQSSGTSLLPKDGAPFSWDSLDEDGLDDSLLELSEGEEDDGDVNYTEEEIDA
  LLKEDDPSYEQSSGEDDGGHVEKGERGSQILLDTPREKNSSYSLGPVAETPDLFKLPQLS
  TSSGHGPAHTKPLNRRSVLEKNLIKVTVAPFNPTVCDALLDKDETDSSKDTEKLSSLGEE
  MREDGLSPNESKLCTESEGISPNNSAWNGPQLSSSNNNFQQTVSDKNMPDSENPTSVFSR
  ISDHSETPNMELSCRNGGSHKSSCEMRSLVVSTSSNKQDVLNKDSGKMKGHERRLGKVIP
  VLQTKTRTNVPTFSQSNLEQQKQLYLRSVIAHIEDPEDTNQGISGELCALMDQVHHMQHS
  KWQHPSDLTTRNYARRQKHLQRYSLTQWVDRNMRSHHRFQRLPDFSYS
• Tissue Specificity: Expressed in brain, spleen, and lung. Not detected in pancreas or liver. In pancreas, expressed predominantly in islet cells and to a lesser extent in acinar cells, but not expressed in ductal cells. Up-regulated in various pancreatic ductal adenocarcinomas and pancreatic intraepithelial neoplasias. Detected in pancreatic ductal adenocarcinoma cells (at protein level). Not detected in non-neoplastic ductal epithelium (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Pancreatic cancer	DISJC981	Strong	Genetic Variation	[2]
Adenocarcinoma	DIS3IHTY	Disputed	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of S100P-binding protein (S100PBP).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of S100P-binding protein (S100PBP).	[7]

5 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 S100P-binding protein (S100PBP).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of S100P-binding protein (S100PBP).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of S100P-binding protein (S100PBP).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of S100P-binding protein (S100PBP).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of S100P-binding protein (S100PBP).	[10]

References

• [1] S100P-binding protein, S100PBP, mediates adhesion through regulation of cathepsin Z in pancreatic cancer cells.Am J Pathol. 2012 Apr;180(4):1485-94. doi: 10.1016/j.ajpath.2011.12.031. Epub 2012 Feb 11.
• [2] Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer.Am J Pathol. 2005 Jan;166(1):81-92. doi: 10.1016/S0002-9440(10)62234-1.
• [3] Usefulness of S100P in diagnosis of adenocarcinoma of pancreas on fine-needle aspiration biopsy specimens.Am J Clin Pathol. 2008 Jan;129(1):81-8. doi: 10.1309/5D76NDE81LE8G545.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.