Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCC370G)

• DOT Name: Rhombotin-2 (LMO2)
• Synonyms: Cysteine-rich protein TTG-2; LIM domain only protein 2; LMO-2; T-cell translocation protein 2
• Gene Name: LMO2
• UniProt ID: RBTN2_HUMAN
• PDB ID: 2XJY; 2XJZ; 2YPA; 4KFZ
• Pfam ID: PF00412
• Sequence:
  MSSAIERKSLDPSEEPVDEVLQIPPSLLTCGGCQQNIGDRYFLKAIDQYWHEDCLSCDLC
  GCRLGEVGRRLYYKLGRKLCRRDYLRLFGQDGLCASCDKRIRAYEMTMRVKDKVYHLECF
  KCAACQKHFCVGDRYLLINSDIVCEQDIYEWTKINGMI
• Function: Acts with TAL1/SCL to regulate red blood cell development. Also acts with LDB1 to maintain erythroid precursors in an immature state.
• KEGG Pathway: Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway: RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)

Molecular Interaction Atlas (MIA) of This DOT

19 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 Rhombotin-2 (LMO2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rhombotin-2 (LMO2).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Rhombotin-2 (LMO2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Rhombotin-2 (LMO2).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Rhombotin-2 (LMO2).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Rhombotin-2 (LMO2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Rhombotin-2 (LMO2).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Rhombotin-2 (LMO2).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Rhombotin-2 (LMO2).	[7]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Rhombotin-2 (LMO2).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Rhombotin-2 (LMO2).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Rhombotin-2 (LMO2).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Rhombotin-2 (LMO2).	[11]
Pomalidomide	DMTGBAX	Approved	Pomalidomide decreases the expression of Rhombotin-2 (LMO2).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Rhombotin-2 (LMO2).	[10]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Rhombotin-2 (LMO2).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rhombotin-2 (LMO2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Rhombotin-2 (LMO2).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Rhombotin-2 (LMO2).	[18]

2 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 Rhombotin-2 (LMO2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Rhombotin-2 (LMO2).	[16]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [4] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [5] 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.
• [6] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] 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.
• [11] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [12] Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood. 2005 May 15;105(10):3833-40. doi: 10.1182/blood-2004-03-0828. Epub 2004 Aug 3.
• [13] Expression of the proto-oncogene rhombotin-2 is identical to the acute phase response protein metallothionein, suggesting multiple functions. Cell Growth Differ. 1995 May;6(5):587-96.
• [14] 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.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] 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.
• [17] 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.
• [18] 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.