Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4PLUU3)

• DOT Name: Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1)
• Synonyms: PRPP synthase-associated protein 1; 39 kDa phosphoribosypyrophosphate synthase-associated protein; PAP39
• Gene Name: PRPSAP1
• Related Disease: Ovarian serous adenocarcinoma
• UniProt ID: KPRA_HUMAN
• PDB ID: 2C4K
• Pfam ID: PF14572 ; PF13793
• Sequence:
  MNAARTGYRVFSANSTAACTELAKRITERLGAELGKSVVYQETNGETRVEIKESVRGQDI
  FIIQTIPRDVNTAVMELLIMAYALKTACARNIIGVIPYFPYSKQSKMRKRGSIVCKLLAS
  MLAKAGLTHIITMDLHQKEIQGFFSFPVDNLRASPFLLQYIQEEIPNYRNAVIVAKSPDA
  AKRAQSYAERLRLGLAVIHGEAQCTELDMDDGRHSPPMVKNATVHPGLELPLMMAKEKPP
  ITVVGDVGGRIAIIVDDIIDDVESFVAAAEILKERGAYKIYVMATHGILSAEAPRLIEES
  SVDEVVVTNTVPHEVQKLQCPKIKTVDISLILSEAIRRIHNGESMAYLFRNITVDD
• Function: Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ovarian serous adenocarcinoma	DISSU72Z	Definitive	Genetic Variation	[1]

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 Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[15]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[16]

3 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 Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[13]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Phosphoribosyl pyrophosphate synthase-associated protein 1 (PRPSAP1).	[13]

References

• [1] Identification of novel epithelial ovarian cancer loci in women of African ancestry.Int J Cancer. 2020 Jun 1;146(11):2987-2998. doi: 10.1002/ijc.32653. Epub 2019 Oct 8.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [14] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [15] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [16] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.