Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXQO55Y)

• DOT Name: Liprin-beta-2 (PPFIBP2)
• Synonyms: Protein tyrosine phosphatase receptor type f polypeptide-interacting protein-binding protein 2; PTPRF-interacting protein-binding protein 2
• Gene Name: PPFIBP2
• Related Disease:
  Prostate carcinoma
  Familial prostate carcinoma
  Intrahepatic cholangiocarcinoma
  Prostate cancer, hereditary, 1
  Congenital contractural arachnodactyly
  Biliary tract cancer
  Neoplasm
  Prostate cancer
  Prostate neoplasm
• UniProt ID: LIPB2_HUMAN
• PDB ID: 3QH9
• Pfam ID: PF00536 ; PF07647
• Sequence:
  MASDASHALEAALEQMDGIIAGTKTGADLSDGTCEPGLASPASYMNPFPVLHLIEDLRLA
  LEMLELPQERAALLSQIPGPTAAYIKEWFEESLSQVNHHSAASNETYQERLARLEGDKES
  LILQVSVLTDQVEAQGEKIRDLEVCLEGHQVKLNAAEEMLQQELLSRTSLETQKLDLMTE
  VSELKLKLVGMEKEQREQEEKQRKAEELLQELRHLKIKVEELENERNQYEWKLKATKAEV
  AQLQEQVALKDAEIERLHSQLSRTAALHSESHTERDQEIQRLKMGMETLLLANEDKDRRI
  EELTGLLNQYRKVKEIVMVTQGPSERTLSINEEEPEGGFSKWNATNKDPEELFKQEMPPR
  CSSPTVGPPPLPQKSLETRAQKKLSCSLEDLRSESVDKCMDGNQPFPVLEPKDSPFLAEH
  KYPTLPGKLSGATPNGEAAKSPPTICQPDATGSSLLRLRDTESGWDDTAVVNDLSSTSSG
  TESGPQSPLTPDGKRNPKGIKKFWGKIRRTQSGNFYTDTLGMAEFRRGGLRATAGPRLSR
  TRDSKGQKSDANAPFAQWSTERVCAWLEDFGLAQYVIFARQWVSSGHTLLTATPQDMEKE
  LGIKHPLHRKKLVLAVKAINTKQEEKSALLDHIWVTRWLDDIGLPQYKDQFHESRVDRRM
  LQYLTVNDLLFLKVTSQLHHLSIKCAIHVLHVNKFNPHCLHRRPADESNLSPSEVVQWSN
  HRVMEWLRSVDLAEYAPNLRGSGVHGGLIILEPRFTGDTLAMLLNIPPQKTLLRRHLTTK
  FNALIGPEAEQEKREKMASPAYTPLTTTAKVRPRKLGFSHFGNIRKKKFDESTDYICPME
  PSDGVSDSHRVYSGYRGLSPLDAPELDGLDQVGQIS
• Function: May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A.
• Tissue Specificity: Widely expressed.
• Reactome Pathway: Receptor-type tyrosine-protein phosphatases (R-HSA-388844)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate carcinoma	DISMJPLE	Definitive	Genetic Variation	[1]
Familial prostate carcinoma	DISL9KNO	Strong	Biomarker	[1]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Biomarker	[2]
Prostate cancer, hereditary, 1	DISE2P4L	Strong	Biomarker	[1]
Congenital contractural arachnodactyly	DISOM1K7	moderate	Biomarker	[3]
Biliary tract cancer	DISBNYQL	Limited	Genetic Variation	[4]
Neoplasm	DISZKGEW	Limited	Altered Expression	[4]
Prostate cancer	DISF190Y	Limited	Genetic Variation	[5]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Liprin-beta-2 (PPFIBP2) affects the response to substance of Progesterone.	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Liprin-beta-2 (PPFIBP2).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Liprin-beta-2 (PPFIBP2).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Liprin-beta-2 (PPFIBP2).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Liprin-beta-2 (PPFIBP2).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Liprin-beta-2 (PPFIBP2).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Liprin-beta-2 (PPFIBP2).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Liprin-beta-2 (PPFIBP2).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Liprin-beta-2 (PPFIBP2).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Liprin-beta-2 (PPFIBP2).	[16]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Liprin-beta-2 (PPFIBP2).	[16]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Liprin-beta-2 (PPFIBP2).	[17]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Liprin-beta-2 (PPFIBP2).	[18]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Liprin-beta-2 (PPFIBP2).	[20]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Liprin-beta-2 (PPFIBP2).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Liprin-beta-2 (PPFIBP2).	[24]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Liprin-beta-2 (PPFIBP2).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Liprin-beta-2 (PPFIBP2).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Liprin-beta-2 (PPFIBP2).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Liprin-beta-2 (PPFIBP2).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Liprin-beta-2 (PPFIBP2).	[23]

References

• [1] Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.Nat Genet. 2018 Jul;50(7):928-936. doi: 10.1038/s41588-018-0142-8. Epub 2018 Jun 11.
• [2] Metformin potentiates the effect of arsenic trioxide suppressing intrahepatic cholangiocarcinoma: roles of p38 MAPK, ERK3, and mTORC1.J Hematol Oncol. 2017 Feb 28;10(1):59. doi: 10.1186/s13045-017-0424-0.
• [3] lncRNA FLVCR1-AS1 regulates cell proliferation, migration and invasion by sponging miR-485-5p in human cholangiocarcinoma.Oncol Lett. 2019 Sep;18(3):2240-2247. doi: 10.3892/ol.2019.10577. Epub 2019 Jul 5.
• [4] Role of crosstalk between interleukin-6 and transforming growth factor-beta 1 in epithelial-mesenchymal transition and chemoresistance in biliary tract cancer.Eur J Cancer. 2013 May;49(7):1725-40. doi: 10.1016/j.ejca.2012.12.002. Epub 2013 Jan 5.
• [5] Germline mutations in PPFIBP2 are associated with lethal prostate cancer.Prostate. 2018 Dec;78(16):1222-1228. doi: 10.1002/pros.23697. Epub 2018 Jul 24.
• [6] Large-scale association analysis in Asians identifies new susceptibility loci for prostate cancer.Nat Commun. 2015 Oct 7;6:8469. doi: 10.1038/ncomms9469.
• [7] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [8] 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.
• [9] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [10] 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.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [14] 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.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [17] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [18] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [23] 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.
• [24] 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.
• [25] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.
• [26] Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study. Environ Health Perspect. 2015 May;123(5):458-66. doi: 10.1289/ehp.1408775. Epub 2015 Jan 13.