Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCY1B1O)

• DOT Name: Ribose-phosphate pyrophosphokinase 2 (PRPS2)
• Synonyms: EC 2.7.6.1; PPRibP; Phosphoribosyl pyrophosphate synthase II; PRS-II
• Gene Name: PRPS2
• Related Disease:
  Advanced cancer
  Male infertility
  Oligospermia
  Systemic lupus erythematosus
• UniProt ID: PRPS2_HUMAN
• PDB ID: 7YK1
• EC Number: 2.7.6.1
• Pfam ID: PF14572 ; PF13793
• Sequence:
  MPNIVLFSGSSHQDLSQRVADRLGLELGKVVTKKFSNQETSVEIGESVRGEDVYIIQSGC
  GEINDNLMELLIMINACKIASSSRVTAVIPCFPYARQDKKDKSRAPISAKLVANMLSVAG
  ADHIITMDLHASQIQGFFDIPVDNLYAEPAVLQWIRENIAEWKNCIIVSPDAGGAKRVTS
  IADRLNVEFALIHKERKKANEVDRMVLVGDVKDRVAILVDDMADTCGTICHAADKLLSAG
  ATKVYAILTHGIFSGPAISRINNAAFEAVVVTNTIPQEDKMKHCTKIQVIDISMILAEAI
  RRTHNGESVSYLFSHVPL
• Function: Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway: 5-Phosphoribose 1-diphosphate biosynthesis (R-HSA-73843)
• BioCyc Pathway: MetaCyc:HS02317-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Oligospermia	DIS6YJF3	Strong	Biomarker	[2]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[11]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[16]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[17]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Ribose-phosphate pyrophosphokinase 2 (PRPS2).	[18]

References

• [1] MYCN promotes neuroblastoma malignancy by establishing a regulatory circuit with transcription factor AP4.Oncotarget. 2016 Aug 23;7(34):54937-54951. doi: 10.18632/oncotarget.10709.
• [2] Phosphoribosyl-pyrophosphate synthetase 2 (PRPS2) depletion regulates spermatogenic cell apoptosis and is correlated with hypospermatogenesis.Asian J Androl. 2020 Sep-Oct;22(5):493-499. doi: 10.4103/aja.aja_122_19.
• [3] Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus.Hum Mol Genet. 2015 Jan 1;24(1):274-84. doi: 10.1093/hmg/ddu429. Epub 2014 Aug 22.
• [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] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] 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.
• [11] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [14] Identification of potential biomarkers for predicting acute dermal irritation by proteomic analysis. J Appl Toxicol. 2011 Nov;31(8):762-72.
• [15] 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.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [18] Evaluation of an in vitro model of androgen ablation and identification of the androgen responsive proteome in LNCaP cells. Proteomics. 2007 Jan;7(1):47-63.