Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6RAJZR)

• DOT Name: L-selectin (SELL)
• Synonyms: CD62 antigen-like family member L; Leukocyte adhesion molecule 1; LAM-1; Leukocyte surface antigen Leu-8; Leukocyte-endothelial cell adhesion molecule 1; LECAM1; Lymph node homing receptor; TQ1; gp90-MEL; CD antigen CD62L
• Gene Name: SELL
• UniProt ID: LYAM1_HUMAN
• PDB ID: 2LGF; 3CFW; 5VC1
• Pfam ID: PF00008 ; PF00059 ; PF00084
• Sequence:
  MIFPWKCQSTQRDLWNIFKLWGWTMLCCDFLAHHGTDCWTYHYSEKPMNWQRARRFCRDN
  YTDLVAIQNKAEIEYLEKTLPFSRSYYWIGIRKIGGIWTWVGTNKSLTEEAENWGDGEPN
  NKKNKEDCVEIYIKRNKDAGKWNDDACHKLKAALCYTASCQPWSCSGHGECVEIINNYTC
  NCDVGYYGPQCQFVIQCEPLEAPELGTMDCTHPLGNFSFSSQCAFSCSEGTNLTGIEETT
  CGPFGNWSSPEPTCQVIQCEPLSAPDLGIMNCSHPLASFSFTSACTFICSEGTELIGKKK
  TICESSGIWSNPSPICQKLDKSFSMIKEGDYNPLFIPVAVMVTAFSGLAFIIWLARRLKK
  GKKSKRSMNDPY
• Function: Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells. Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Promotes initial tethering and rolling of leukocytes in endothelia.
• Tissue Specificity: Expressed in B-cell lines and T-lymphocytes.
• KEGG Pathway: Cell adhesion molecules (hsa04514)
• Reactome Pathway:
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Neutrophil degranulation (R-HSA-6798695)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DOT

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 L-selectin (SELL).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of L-selectin (SELL).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of L-selectin (SELL).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of L-selectin (SELL).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of L-selectin (SELL).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of L-selectin (SELL).	[5]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of L-selectin (SELL).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of L-selectin (SELL).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of L-selectin (SELL).	[8]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of L-selectin (SELL).	[9]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of L-selectin (SELL).	[10]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the expression of L-selectin (SELL).	[10]
Piroxicam	DMTK234	Approved	Piroxicam affects the expression of L-selectin (SELL).	[10]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of L-selectin (SELL).	[11]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of L-selectin (SELL).	[12]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of L-selectin (SELL).	[13]
Flurbiprofen	DMGN4BY	Approved	Flurbiprofen decreases the expression of L-selectin (SELL).	[10]
Mefenamic acid	DMK7HFI	Approved	Mefenamic acid decreases the expression of L-selectin (SELL).	[10]
Erythromycin	DM4K7GQ	Approved	Erythromycin increases the expression of L-selectin (SELL).	[14]
Ketoprofen	DMRKXPT	Approved	Ketoprofen decreases the expression of L-selectin (SELL).	[10]
Flufenamic Acid	DMC8VNH	Approved	Flufenamic Acid decreases the expression of L-selectin (SELL).	[10]
Meclofenamic acid	DM05FXR	Approved	Meclofenamic acid decreases the expression of L-selectin (SELL).	[10]
Meloxicam	DM2AR7L	Approved	Meloxicam affects the expression of L-selectin (SELL).	[10]
Iloprost	DMVPZBE	Approved	Iloprost decreases the expression of L-selectin (SELL).	[15]
Griseofulvin	DMK54YG	Approved	Griseofulvin decreases the expression of L-selectin (SELL).	[16]
Nabumetone	DMAT2XH	Approved	Nabumetone affects the expression of L-selectin (SELL).	[10]
Phenylbutazone	DMAYL0T	Approved	Phenylbutazone affects the expression of L-selectin (SELL).	[10]
Aceclofenac	DMZDF0B	Approved	Aceclofenac decreases the expression of L-selectin (SELL).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of L-selectin (SELL).	[3]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of L-selectin (SELL).	[17]
D-7193	DMO9HWU	Discontinued in Phase 2	D-7193 decreases the expression of L-selectin (SELL).	[19]
Nimesulide	DMR1NMD	Terminated	Nimesulide decreases the expression of L-selectin (SELL).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of L-selectin (SELL).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of L-selectin (SELL).	[21]
Rutin	DMEHRAJ	Investigative	Rutin increases the expression of L-selectin (SELL).	[22]
Edetic acid	DM10D85	Investigative	Edetic acid decreases the expression of L-selectin (SELL).	[13]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PAF	DMRZAQW	Investigative	PAF increases the secretion of L-selectin (SELL).	[23]

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] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [6] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [7] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [8] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [9] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [10] Structure-function relationship and role of tumor necrosis factor-alpha-converting enzyme in the down-regulation of L-selectin by non-steroidal anti-inflammatory drugs. J Biol Chem. 2002 Oct 11;277(41):38212-21. doi: 10.1074/jbc.M205142200. Epub 2002 Jul 29.
• [11] Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils. J Biol Chem. 2002 Jul 19;277(29):26012-20. doi: 10.1074/jbc.M201803200. Epub 2002 Apr 29.
• [12] Immunological consequences of thalidomide treatment in Sj?gren's syndrome. Ann Rheum Dis. 2006 Jan;65(1):112-4. doi: 10.1136/ard.2005.038406.
• [13] Effect of heparin anticoagulation on neutrophil adhesion molecules and release of IL8: C3 is not essential. Cardiovasc Res. 1995 Nov;30(5):676-81. doi: 10.1016/0008-6363(95)00069-0.
• [14] The in vitro effects of quinupristin/dalfopristin, erythromycin and levofloxacin at low concentrations on the expression of different cell adhesion molecules on the surface of endothelial cells (Eahy926). Toxicology. 2006 Jan 20;218(1):30-8. doi: 10.1016/j.tox.2005.09.014. Epub 2005 Nov 16.
• [15] The response of skin perfusion and of rheological and immunological variables to intravenous prostanoid administration in Raynaud's phenomenon secondary to collagenosis. Vasa. 2005 Nov;34(4):243-9. doi: 10.1024/0301-1526.34.4.243.
• [16] Griseofulvin has a potential to modulate the expression of cell adhesion molecules on leukocytes and vascular endothelial cells. Int Immunopharmacol. 2001 Jan;1(1):75-83. doi: 10.1016/s0162-3109(00)00266-6.
• [17] Regulation of aryl hydrocarbon receptor function by selective estrogen receptor modulators. Mol Endocrinol. 2010 Jan;24(1):33-46.
• [18] 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.
• [19] The new oral immunomodulating drug DiNAC induces brachial artery vasodilatation at rest and during hyperemia in hypercholesterolemic subjects, likely by a nitric oxide-dependent mechanism. Atherosclerosis. 2008 Jan;196(1):275-282. doi: 10.1016/j.atherosclerosis.2006.10.031. Epub 2006 Dec 8.
• [20] Effect of bisphenol A on human neutrophils immunophenotype. Sci Rep. 2020 Feb 20;10(1):3083. doi: 10.1038/s41598-020-59753-2.
• [21] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [22] Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells. J Nutr. 2004 Oct;134(10):2509-16.
• [23] Effect of theophylline on CD11b and L-selectin expression and density of eosinophils and neutrophils in vitro. Eur Respir J. 1998 Sep;12(3):585-91. doi: 10.1183/09031936.98.12030585.