Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT83O8WI)

• DOT Name: Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1)
• Synonyms: EPS8-like protein 1; Epidermal growth factor receptor pathway substrate 8-related protein 1; EPS8-related protein 1
• Gene Name: EPS8L1
• Related Disease: Glioma
• UniProt ID: ES8L1_HUMAN
• PDB ID: 2K2M; 2ROL
• Pfam ID: PF08416 ; PF18016 ; PF00018
• Sequence:
  MSTATGPEAAPKPSAKSIYEQRKRYSTVVMADVSQYPVNHLVTFCLGEDDGVHTVEDASR
  KLAVMDSQGRVWAQEMLLRVSPDHVTLLDPASKEELESYPLGAIVRCDAVMPPGRSRSLL
  LLVCQEPERAQPDVHFFQGLRLGAELIREDIQGALHNYRSGRGERRAAALRATQEELQRD
  RSPAAETPPLQRRPSVRAVISTVERGAGRGRPQAKPIPEAEEAQRPEPVGTSSNADSASP
  DLGPRGPDLAVLQAEREVDILNHVFDDVESFVSRLQKSAEAARVLEHRERGRRSRRRAAG
  EGLLTLRAKPPSEAEYTDVLQKIKYAFSLLARLRGNIADPSSPELLHFLFGPLQMIVNTS
  GGPEFASSVRRPHLTSDAVALLRDNVTPRENELWTSLGDSWTRPGLELSPEEGPPYRPEF
  FSGWEPPVTDPQSRAWEDPVEKQLQHERRRRQQSAPQVAVNGHRDLEPESEPQLESETAG
  KWVLCNYDFQARNSSELSVKQRDVLEVLDDSRKWWKVRDPAGQEGYVPYNILTPYPGPRL
  HHSQSPARSLNSTPPPPPAPAPAPPPALARPRWDRPRWDSCDSLNGLDPSEKEKFSQMLI
  VNEELQARLAQGRSGPSRAVPGPRAPEPQLSPGSDASEVRAWLQAKGFSSGTVDALGVLT
  GAQLFSLQKEELRAVSPEEGARVYSQVTVQRSLLEDKEKVSELEAVMEKQKKKVEGEVEM
  EVI
• Function: Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton.
• Tissue Specificity: Detected in placenta.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[3]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[4]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[6]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[7]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[12]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[13]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Epidermal growth factor receptor kinase substrate 8-like protein 1 (EPS8L1).	[9]

References

• [1] Screening and functional analysis ofgliomarelated genes induced by candoxin.Mol Med Rep. 2014 Aug;10(2):767-72. doi: 10.3892/mmr.2014.2311. Epub 2014 Jun 10.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] 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.
• [6] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [7] Malathion induced cancer-linked gene expression in human lymphocytes. Environ Res. 2020 Mar;182:109131. doi: 10.1016/j.envres.2020.109131. Epub 2020 Jan 10.
• [8] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [9] 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.
• [10] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.