Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF518AI)

• DOT Name: Endothelial cell-selective adhesion molecule (ESAM)
• Gene Name: ESAM
• Related Disease:
  Anemia
  Arteriosclerosis
  Atherosclerosis
  Chronic kidney disease
  Diabetic kidney disease
  Immunodeficiency
  leukaemia
  Leukemia
  Metastatic malignant neoplasm
  Neoplasm
  Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity
  Pneumonia
  Pneumonitis
  Schizophrenia
  Chronic obstructive pulmonary disease
  Arrhythmia
• UniProt ID: ESAM_HUMAN
• Pfam ID: PF13927 ; PF07686
• Sequence:
  MISLPGPLVTNLLRFLFLGLSALAPPSRAQLQLHLPANRLQAVEGGEVVLPAWYTLHGEV
  SSSQPWEVPFVMWFFKQKEKEDQVLSYINGVTTSKPGVSLVYSMPSRNLSLRLEGLQEKD
  SGPYSCSVNVQDKQGKSRGHSIKTLELNVLVPPAPPSCRLQGVPHVGANVTLSCQSPRSK
  PAVQYQWDRQLPSFQTFFAPALDVIRGSLSLTNLSSSMAGVYVCKAHNEVGTAQCNVTLE
  VSTGPGAAVVAGAVVGTLVGLGLLAGLVLLYHRRGKALEEPANDIKEDAIAPRTLPWPKS
  SDTISKNGTLSSVTSARALRPPHGPPRPGALTPTPSLSSQALPSPRLPTTDGAHPQPISP
  IPGGVSSSGLSRMGAVPVMVPAQSQAGSLV
• Function: Can mediate aggregation most likely through a homophilic molecular interaction.
• Tissue Specificity: Highly expressed in endothelial cells.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Leukocyte transendothelial migration (hsa04670)
• Reactome Pathway: Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anemia	DISTVL0C	Strong	Genetic Variation	[1]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[2]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[2]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[3]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[4]
Immunodeficiency	DIS093I0	Strong	Biomarker	[5]
leukaemia	DISS7D1V	Strong	Biomarker	[5]
Leukemia	DISNAKFL	Strong	Biomarker	[5]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity	DIS36FUT	Strong	Autosomal recessive	[7]
Pneumonia	DIS8EF3M	Strong	Altered Expression	[8]
Pneumonitis	DIS88E0K	Strong	Altered Expression	[8]
Schizophrenia	DISSRV2N	Strong	Biomarker	[9]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[10]
Arrhythmia	DISFF2NI	Limited	Biomarker	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[15]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Endothelial cell-selective adhesion molecule (ESAM).	[20]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[21]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Endothelial cell-selective adhesion molecule (ESAM).	[22]

References

• [1] Endothelial Cell-Selective Adhesion Molecule Contributes to the Development of Definitive Hematopoiesis in the Fetal Liver.Stem Cell Reports. 2019 Dec 10;13(6):992-1005. doi: 10.1016/j.stemcr.2019.11.002.
• [2] Soluble endothelial cell-selective adhesion molecule and incident cardiovascular events in a multiethnic population.Am Heart J. 2017 Sep;191:55-61. doi: 10.1016/j.ahj.2017.06.008. Epub 2017 Jun 23.
• [3] Adiponectin is related to markers of endothelial dysfunction and neoangiogenesis in diabetic patients.Int Urol Nephrol. 2018 Sep;50(9):1661-1666. doi: 10.1007/s11255-018-1890-1. Epub 2018 May 26.
• [4] Endothelial cell-selective adhesion molecule regulates albuminuria in diabetic nephropathy.Microvasc Res. 2009 May;77(3):348-55. doi: 10.1016/j.mvr.2009.01.002. Epub 2009 Jan 24.
• [5] ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.Exp Hematol. 2016 Apr;44(4):269-81.e1. doi: 10.1016/j.exphem.2015.12.010. Epub 2016 Jan 14.
• [6] Role of endothelial cell-selective adhesion molecule in hematogeneous metastasis.Microvasc Res. 2010 Jul;80(1):133-41. doi: 10.1016/j.mvr.2010.02.006. Epub 2010 Feb 11.
• [7] Bi-allelic variants in the ESAM tight-junction gene cause a neurodevelopmental disorder associated with fetal intracranial hemorrhage. Am J Hum Genet. 2023 Apr 6;110(4):681-690. doi: 10.1016/j.ajhg.2023.03.005. Epub 2023 Mar 29.
• [8] NOX2 in lung inflammation: quantum dot based in situ imaging of NOX2-mediated expression of vascular cell adhesion molecule-1.Am J Physiol Lung Cell Mol Physiol. 2014 Feb;306(3):L260-8. doi: 10.1152/ajplung.00278.2013. Epub 2013 Dec 6.
• [9] Exome sequencing supports a de novo mutational paradigm for schizophrenia.Nat Genet. 2011 Aug 7;43(9):864-8. doi: 10.1038/ng.902.
• [10] Endothelial cell adhesion molecule CD146: implications for its role in the pathogenesis of COPD.J Pathol. 2013 Aug;230(4):388-98. doi: 10.1002/path.4197.
• [11] Pre-operative serum VCAM-1 as a biomarker of atrial fibrillation after coronary artery bypass grafting.J Cardiothorac Surg. 2017 Aug 18;12(1):70. doi: 10.1186/s13019-017-0632-2.
• [12] 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.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] 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.
• [19] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [20] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [21] 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.
• [22] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.