Details of Drug Off-Target (DOT)

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

• DOT Name: Lymphocyte function-associated antigen 3 (CD58)
• Synonyms: Ag3; Surface glycoprotein LFA-3; CD antigen CD58
• Gene Name: CD58
• UniProt ID: LFA3_HUMAN
• PDB ID: 1CCZ; 1CI5; 1QA9
• Sequence:
  MVAGSDAGRALGVLSVVCLLHCFGFISCFSQQIYGVVYGNVTFHVPSNVPLKEVLWKKQK
  DKVAELENSEFRAFSSFKNRVYLDTVSGSLTIYNLTSSDEDEYEMESPNITDTMKFFLYV
  LESLPSPTLTCALTNGSIEVQCMIPEHYNSHRGLIMYSWDCPMEQCKRNSTSIYFKMEND
  LPQKIQCTLSNPLFNTTSSIILTTCIPSSGHSRHRYALIPIPLAVITTCIVLYMNGILKC
  DRKPDRTNSN
• Function: Ligand of the T-lymphocyte CD2 glycoprotein. This interaction is important in mediating thymocyte interactions with thymic epithelial cells, antigen-independent and -dependent interactions of T-lymphocytes with target cells and antigen-presenting cells and the T-lymphocyte rosetting with erythrocytes. In addition, the LFA-3/CD2 interaction may prime response by both the CD2+ and LFA-3+ cells.
• KEGG Pathway:
  Cell adhesion molecules (hsa04514)
  Epstein-Barr virus infection (hsa05169)
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  Cell surface interactions at the vascular wall (R-HSA-202733)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Lymphocyte function-associated antigen 3 (CD58) affects the response to substance of Mitoxantrone.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Lymphocyte function-associated antigen 3 (CD58).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Lymphocyte function-associated antigen 3 (CD58).	[9]

18 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 Lymphocyte function-associated antigen 3 (CD58).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lymphocyte function-associated antigen 3 (CD58).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lymphocyte function-associated antigen 3 (CD58).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lymphocyte function-associated antigen 3 (CD58).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lymphocyte function-associated antigen 3 (CD58).	[8]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Lymphocyte function-associated antigen 3 (CD58).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Lymphocyte function-associated antigen 3 (CD58).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[14]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Lymphocyte function-associated antigen 3 (CD58).	[15]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Lymphocyte function-associated antigen 3 (CD58).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[17]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Lymphocyte function-associated antigen 3 (CD58).	[18]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [9] Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women. Arch Toxicol. 2017 May;91(5):2067-2078. doi: 10.1007/s00204-016-1879-4. Epub 2016 Nov 12.
• [10] 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.
• [11] 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.
• [12] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] 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.
• [15] Regulation of lipocalin-2 gene by the cancer chemopreventive retinoid 4-HPR. Int J Cancer. 2006 Oct 1;119(7):1599-606.
• [16] 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.
• [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] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [19] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.