Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW0ZI4D)

• DOT Name: Homeobox protein GBX-2 (GBX2)
• Synonyms: Gastrulation and brain-specific homeobox protein 2
• Gene Name: GBX2
• Related Disease:
  Advanced cancer
  Amyotrophic lateral sclerosis type 1
  Breast cancer
  Breast carcinoma
  Familial amyotrophic lateral sclerosis
  Lung adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Usher syndrome
  Laryngeal squamous cell carcinoma
  Neoplasm
  Acute myelogenous leukaemia
• UniProt ID: GBX2_HUMAN
• Pfam ID: PF00046
• Sequence:
  MSAAFPPSLMMMQRPLGSSTAFSIDSLIGSPPQPSPGHFVYTGYPMFMPYRPVVLPPPPP
  PPPALPQAALQPALPPAHPHHQIPSLPTGFCSSLAQGMALTSTLMATLPGGFSASPQHQE
  AAAARKFAPQPLPGGGNFDKAEALQADAEDGKGFLAKEGSLLAFSAAETVQASLVGAVRG
  QGKDESKVEDDPKGKEESFSLESDVDYSSDDNLTGQAAHKEEDPGHALEETPPSSGAAGS
  TTSTGKNRRRRTAFTSEQLLELEKEFHCKKYLSLTERSQIAHALKLSEVQVKIWFQNRRA
  KWKRVKAGNANSKTGEPSRNPKIVVPIPVHVSRFAIRSQHQQLEQARP
• Function: May act as a transcription factor for cell pluripotency and differentiation in the embryo.
• Reactome Pathway:
  Formation of the posterior neural plate (R-HSA-9832991)
  Formation of the anterior neural plate (R-HSA-9823739)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[1]
Familial amyotrophic lateral sclerosis	DISWZ9CJ	Strong	Biomarker	[2]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[3]
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[1]
Usher syndrome	DIS9YIS7	Strong	Biomarker	[4]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[5]
Neoplasm	DISZKGEW	moderate	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[6]

10 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 Homeobox protein GBX-2 (GBX2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Homeobox protein GBX-2 (GBX2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Homeobox protein GBX-2 (GBX2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Homeobox protein GBX-2 (GBX2).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Homeobox protein GBX-2 (GBX2).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Homeobox protein GBX-2 (GBX2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Homeobox protein GBX-2 (GBX2).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Homeobox protein GBX-2 (GBX2).	[14]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Homeobox protein GBX-2 (GBX2).	[15]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Homeobox protein GBX-2 (GBX2).	[16]

1 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 increases the methylation of Homeobox protein GBX-2 (GBX2).	[12]

References

• [1] Downregulated GBX2 gene suppresses proliferation, invasion and angiogenesis of breast cancer cells through inhibiting the Wnt/-catenin signaling pathway.Cancer Biomark. 2018;23(3):405-418. doi: 10.3233/CBM-181466.
• [2] Differential expression of inflammation- and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis.J Neurochem. 2002 Jan;80(1):158-67. doi: 10.1046/j.0022-3042.2001.00683.x.
• [3] GBX2, as a tumor promoter in lung adenocarcinoma, enhances cells viability, invasion and migration by regulating the AKT/ERK signaling pathway.J Gene Med. 2020 Feb;22(2):e3147. doi: 10.1002/jgm.3147. Epub 2019 Dec 20.
• [4] Elongation factor 1 alpha1 and genes associated with Usher syndromes are downstream targets of GBX2.PLoS One. 2012;7(11):e47366. doi: 10.1371/journal.pone.0047366. Epub 2012 Nov 8.
• [5] MicroRNA-4497 functions as a tumor suppressor in laryngeal squamous cell carcinoma via negatively modulation the GBX2.Auris Nasus Larynx. 2019 Feb;46(1):106-113. doi: 10.1016/j.anl.2018.05.005. Epub 2018 May 26.
• [6] Activation of HLXB9 by juxtaposition with MYB via formation of t(6;7)(q23;q36) in an AML-M4 cell line (GDM-1).Genes Chromosomes Cancer. 2005 Feb;42(2):170-8. doi: 10.1002/gcc.20113.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] 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.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [11] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [12] 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.
• [13] Transcriptomic?pathway?and?benchmark dose analysis of Bisphenol A, Bisphenol S, Bisphenol F, and 3,3',5,5'-Tetrabromobisphenol A in H9 human embryonic stem cells. Toxicol In Vitro. 2021 Apr;72:105097. doi: 10.1016/j.tiv.2021.105097. Epub 2021 Jan 18.
• [14] 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.
• [15] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [16] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.