Details of Drug Off-Target (DOT)

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

• DOT Name: Pre-B-cell leukemia transcription factor 2 (PBX2)
• Synonyms: Homeobox protein PBX2; Protein G17
• Gene Name: PBX2
• Related Disease:
  Acute myelogenous leukaemia
  Classic Hodgkin lymphoma
  Non-small-cell lung cancer
  Acute erythroid leukemia
  Age-related macular degeneration
  Allergic rhinitis
  Asthma
  Epstein barr virus infection
  Neovascular age-related macular degeneration
  Rheumatoid arthritis
  Schizophrenia
  Wilms tumor
  Melanoma
  Lung cancer
  Lung carcinoma
  Systemic lupus erythematosus
  T-cell acute lymphoblastic leukaemia
• UniProt ID: PBX2_HUMAN
• Pfam ID: PF05920 ; PF03792
• Sequence:
  MDERLLGPPPPGGGRGGLGLVSGEPGGPGEPPGGGDPGGGSGGVPGGRGKQDIGDILQQI
  MTITDQSLDEAQAKKHALNCHRMKPALFSVLCEIKEKTGLSIRSSQEEEPVDPQLMRLDN
  MLLAEGVAGPEKGGGSAAAAAAAAASGGGVSPDNSIEHSDYRSKLAQIRHIYHSELEKYE
  QACNEFTTHVMNLLREQSRTRPVAPKEMERMVSIIHRKFSAIQMQLKQSTCEAVMILRSR
  FLDARRKRRNFSKQATEVLNEYFYSHLSNPYPSEEAKEELAKKCGITVSQVSNWFGNKRI
  RYKKNIGKFQEEANIYAVKTAVSVTQGGHSRTSSPTPPSSAGSGGSFNLSGSGDMFLGMP
  GLNGDSYSASQVESLRHSMGPGGYGDNLGGGQMYSPREMRANGSWQEAVTPSSVTSPTEG
  PGSVHSDTSN
• Function: Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'. Activates transcription of PF4 in complex with MEIS1.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Biomarker	[1]
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Genetic Variation	[2]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[3]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[4]
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[5]
Allergic rhinitis	DIS3U9HN	Strong	Genetic Variation	[6]
Asthma	DISW9QNS	Strong	Biomarker	[6]
Epstein barr virus infection	DISOO0WT	Strong	Genetic Variation	[7]
Neovascular age-related macular degeneration	DIS5S9R7	Strong	Genetic Variation	[5]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[8]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[9]
Wilms tumor	DISB6T16	Strong	Altered Expression	[10]
Melanoma	DIS1RRCY	moderate	Biomarker	[11]
Lung cancer	DISCM4YA	Limited	Biomarker	[12]
Lung carcinoma	DISTR26C	Limited	Biomarker	[12]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[13]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Altered Expression	[14]

12 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 Pre-B-cell leukemia transcription factor 2 (PBX2).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[21]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[22]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[24]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[26]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of Pre-B-cell leukemia transcription factor 2 (PBX2).	[28]

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 Pre-B-cell leukemia transcription factor 2 (PBX2).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pre-B-cell leukemia transcription factor 2 (PBX2).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Pre-B-cell leukemia transcription factor 2 (PBX2).	[27]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Pre-B-cell leukemia transcription factor 2 (PBX2).	[27]

References

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• [2] Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin's lymphoma.Nat Commun. 2013;4:2549. doi: 10.1038/ncomms3549.
• [3] Prognostic significance of pre B cell leukemia transcription factor 2 (PBX2) expression in non-small cell lung carcinoma.Cancer Sci. 2009 Jul;100(7):1198-209. doi: 10.1111/j.1349-7006.2009.01156.x. Epub 2009 Mar 12.
• [4] Antiproliferative effect of upregulation of hsa-let-7c-5p in human acute erythroleukemia cells.Cytotechnology. 2018 Dec;70(6):1509-1518. doi: 10.1007/s10616-018-0241-5. Epub 2018 Aug 2.
• [5] A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.Nat Genet. 2016 Feb;48(2):134-43. doi: 10.1038/ng.3448. Epub 2015 Dec 21.
• [6] Variant of PBX2 gene in the 6p21.3 asthma susceptibility locus is associated with allergic rhinitis in Chinese subjects.Int Forum Allergy Rhinol. 2016 May;6(5):537-43. doi: 10.1002/alr.21725. Epub 2016 Feb 8.
• [7] A genome-wide integrative genomic study localizes genetic factors influencing antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA-1).PLoS Genet. 2013;9(1):e1003147. doi: 10.1371/journal.pgen.1003147. Epub 2013 Jan 10.
• [8] A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.Ann Rheum Dis. 2011 Feb;70(2):259-65. doi: 10.1136/ard.2009.126821. Epub 2010 Dec 14.
• [9] Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.Mol Autism. 2017 May 22;8:21. doi: 10.1186/s13229-017-0137-9. eCollection 2017.
• [10] Nephroblastomas show low expression of microR-204 and high expression of its target, the oncogenic transcription factor MEIS1.Pediatr Dev Pathol. 2014 May-Jun;17(3):169-75. doi: 10.2350/13-01-1288-OA.1. Epub 2014 Mar 11.
• [11] The abrogation of the HOXB7/PBX2 complex induces apoptosis in melanoma through the miR-221&222-c-FOS pathway.Int J Cancer. 2013 Aug 15;133(4):879-92. doi: 10.1002/ijc.28097. Epub 2013 Mar 13.
• [12] MicroRNA?915?p prevents the apoptosis of lung cancer cells by downregulating DRG2 and PBX2.Mol Med Rep. 2016 Jan;13(1):505-12. doi: 10.3892/mmr.2015.4565. Epub 2015 Nov 13.
• [13] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [14] TALE homeoproteins as HOX11-interacting partners in T-cell leukemia.Leuk Lymphoma. 2000 Oct;39(3-4):241-56. doi: 10.3109/10428190009065824.
• [15] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [16] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [22] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [23] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [24] 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.
• [25] 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.
• [26] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [27] 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.
• [28] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.