Details of Drug Off-Target (DOT)

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

• DOT Name: Pre-B-cell leukemia transcription factor 4 (PBX4)
• Synonyms: Homeobox protein PBX4
• Gene Name: PBX4
• Related Disease:
  Acute lymphocytic leukaemia
  Childhood acute lymphoblastic leukemia
  Non-insulin dependent diabetes
• UniProt ID: PBX4_HUMAN
• Pfam ID: PF05920 ; PF03792
• Sequence:
  MAAPPRPAPSPPAPRRLDTSDVLQQIMAITDQSLDEAQARKHALNCHRMKPALFSVLCEI
  KEKTVVSIRGIQDEDPPDAQLLRLDNMLLAEGVCRPEKRGRGGAVARAGTATPGGCPNDN
  SIEHSDYRAKLSQIRQIYHSELEKYEQACREFTTHVTNLLQEQSRMRPVSPKEIERMVGA
  IHGKFSAIQMQLKQSTCEAVMTLRSRLLDARRKRRNFSKQATEVLNEYFYSHLNNPYPSE
  EAKEELARKGGLTISQVSNWFGNKRIRYKKNMGKFQEEATIYTGKTAVDTTEVGVPGNHA
  SCLSTPSSGSSGPFPLPSAGDAFLTLRTLASLQPPPGGGCLQSQAQGSWQGATPQPATAS
  PAGDPGSINSSTSN

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute lymphocytic leukaemia	DISPX75S	Strong	Altered Expression	[1]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[2]

3 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 4 (PBX4).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pre-B-cell leukemia transcription factor 4 (PBX4).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Pre-B-cell leukemia transcription factor 4 (PBX4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Pre-B-cell leukemia transcription factor 4 (PBX4).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Pre-B-cell leukemia transcription factor 4 (PBX4).	[5]

References

• [1] MEIS1, PREP1, and PBX4 are differentially expressed in acute lymphoblastic leukemia: association of MEIS1 expression with higher proliferation and chemotherapy resistance.J Exp Clin Cancer Res. 2011 Dec 20;30(1):112. doi: 10.1186/1756-9966-30-112.
• [2] Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.Clin Pharmacol Ther. 2018 Apr;103(4):712-721. doi: 10.1002/cpt.798. Epub 2017 Nov 3.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.