Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD4S36H)

DOT Name	Semaphorin-3E (SEMA3E)
Gene Name	SEMA3E
Related Disease	Adult glioblastoma ( ) Advanced cancer ( ) Allergic asthma ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Capillary hemangioma ( ) Colitis ( ) Colorectal carcinoma ( ) Endometriosis ( ) Gastric cancer ( ) Glioblastoma multiforme ( ) Melanoma ( ) Metastatic malignant neoplasm ( ) Metastatic melanoma ( ) Neoplasm ( ) Stomach cancer ( ) Systemic sclerosis ( ) Ulcerative colitis ( ) Age-related macular degeneration ( ) Glycogen storage disease type II ( ) Hereditary gingival fibromatosis ( ) Prostate cancer ( ) Prostate carcinoma ( ) Asthma ( ) CHARGE syndrome ( ) Kallmann syndrome ( ) Obesity ( ) Stroke ( ) Type-1/2 diabetes ( )
UniProt ID	SEM3E_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00047 ; PF01403
Sequence	MASAGHIITLLLWGYLLELWTGGHTADTTHPRLRLSHKELLNLNRTSIFHSPFGFLDLHT MLLDEYQERLFVGGRDLVYSLSLERISDGYKEIHWPSTALKMEECIMKGKDAGECANYVR VLHHYNRTHLLTCGTGAFDPVCAFIRVGYHLEDPLFHLESPRSERGRGRCPFDPSSSFIS TLIGSELFAGLYSDYWSRDAAIFRSMGRLAHIRTEHDDERLLKEPKFVGSYMIPDNEDRD DNKVYFFFTEKALEAENNAHAIYTRVGRLCVNDVGGQRILVNKWSTFLKARLVCSVPGMN GIDTYFDELEDVFLLPTRDHKNPVIFGLFNTTSNIFRGHAICVYHMSSIRAAFNGPYAHK EGPEYHWSVYEGKVPYPRPGSCASKVNGGRYGTTKDYPDDAIRFARSHPLMYQAIKPAHK KPILVKTDGKYNLKQIAVDRVEAEDGQYDVLFIGTDNGIVLKVITIYNQEMESMEEVILE ELQIFKDPVPIISMEISSKRQQLYIGSASAVAQVRFHHCDMYGSACADCCLARDPYCAWD GISCSRYYPTGTHAKRRFRRQDVRHGNAAQQCFGQQFVGDALDKTEEHLAYGIENNSTLL ECTPRSLQAKVIWFVQKGRETRKEEVKTDDRVVKMDLGLLFLRLHKSDAGTYFCQTVEHS FVHTVRKITLEVVEEEKVEDMFNKDDEEDRHHRMPCPAQSSISQGAKPWYKEFLQLIGYS NFQRVEEYCEKVWCTDRKRKKLKMSPSKWKYANPQEKKLRSKPEHYRLPRHTLDS
Function	Plays an important role in signaling via the cell surface receptor PLXND1. Mediates reorganization of the actin cytoskeleton, leading to the retraction of cell projections. Promotes focal adhesion disassembly and inhibits adhesion of endothelial cells to the extracellular matrix. Regulates angiogenesis, both during embryogenesis and after birth. Can down-regulate sprouting angiogenesis. Required for normal vascular patterning during embryogenesis. Plays an important role in ensuring the specificity of synapse formation.
KEGG Pathway	Axon guidance (hsa04360 )
Reactome Pathway	Other semaphorin interactions (R-HSA-416700 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Allergic asthma	DISHF0H3	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[4]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[4]
Capillary hemangioma	DISQ8XPT	Strong	Biomarker	[5]
Colitis	DISAF7DD	Strong	Genetic Variation	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[7]
Endometriosis	DISX1AG8	Strong	Biomarker	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Melanoma	DIS1RRCY	Strong	Altered Expression	[10]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[11]
Metastatic melanoma	DISSL43L	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[7]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[4]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[12]
Age-related macular degeneration	DIS0XS2C	moderate	Biomarker	[13]
Glycogen storage disease type II	DISXZPBC	moderate	Biomarker	[13]
Hereditary gingival fibromatosis	DISN1ML3	moderate	Biomarker	[13]
Prostate cancer	DISF190Y	moderate	Biomarker	[14]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[14]
Asthma	DISW9QNS	Limited	Biomarker	[15]
CHARGE syndrome	DISKD3CW	Limited	Autosomal dominant	[16]
Kallmann syndrome	DISO3HDG	Limited	Autosomal dominant	[16]
Obesity	DIS47Y1K	Limited	Biomarker	[17]
Stroke	DISX6UHX	Limited	Biomarker	[18]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[17]
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⏷ Show the Full List of 29 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Semaphorin-3E (SEMA3E).	[19]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Semaphorin-3E (SEMA3E).	[20]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Semaphorin-3E (SEMA3E).	[21]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Semaphorin-3E (SEMA3E).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Semaphorin-3E (SEMA3E).	[23]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Semaphorin-3E (SEMA3E).	[24]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Semaphorin-3E (SEMA3E).	[25]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Semaphorin-3E (SEMA3E).	[26]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Semaphorin-3E (SEMA3E).	[27]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Semaphorin-3E (SEMA3E).	[25]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Semaphorin-3E (SEMA3E).	[28]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Semaphorin-3E (SEMA3E).	[25]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Semaphorin-3E (SEMA3E).	[25]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Semaphorin-3E (SEMA3E).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Semaphorin-3E (SEMA3E).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Semaphorin-3E (SEMA3E).	[32]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Semaphorin-3E (SEMA3E).	[33]
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⏷ Show the Full List of 17 Drug(s)

1 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 affects the methylation of Semaphorin-3E (SEMA3E).	[29]
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References

1	Semaphorin-3D and semaphorin-3E inhibit the development of tumors from glioblastoma cells implanted in the cortex of the brain.PLoS One. 2012;7(8):e42912. doi: 10.1371/journal.pone.0042912. Epub 2012 Aug 24.
2	Tumour growth inhibition and anti-metastatic activity of a mutated furin-resistant Semaphorin 3E isoform.EMBO Mol Med. 2012 Mar;4(3):234-50. doi: 10.1002/emmm.201100205. Epub 2012 Jan 13.
3	Semaphorin 3E Inhibits House Dust Mite-Induced Angiogenesis in a Mouse Model of Allergic Asthma.Am J Pathol. 2019 Apr;189(4):762-772. doi: 10.1016/j.ajpath.2019.01.008. Epub 2019 Jan 31.
4	A trimetallic CuAuPd nanowire as a multifunctional nanocomposites applied to ultrasensitive electrochemical detection of Sema3E.Biosens Bioelectron. 2019 Dec 1;145:111677. doi: 10.1016/j.bios.2019.111677. Epub 2019 Sep 6.
5	Infantile hemangioma-derived stem cells and endothelial cells are inhibited by class 3 semaphorins.Biochem Biophys Res Commun. 2015 Aug 14;464(1):126-32. doi: 10.1016/j.bbrc.2015.06.087. Epub 2015 Jun 15.
6	Semaphorin 3E regulates apoptosis in the intestinal epithelium during the development of colitis.Biochem Pharmacol. 2019 Aug;166:264-273. doi: 10.1016/j.bcp.2019.05.029. Epub 2019 Jun 3.
7	MiR-4282 suppresses proliferation and mobility of human colorectal carcinoma cells by targeting semaphorin 3E.Panminerva Med. 2016 Sep;58(3):197-205. Epub 2016 Apr 27.
8	The Expression and Cellular Localisation of Neurotrophin and Neural Guidance Molecules in Peritoneal Ectopic Lesions.Mol Neurobiol. 2019 Jun;56(6):4013-4022. doi: 10.1007/s12035-018-1348-6. Epub 2018 Sep 25.
9	Enhanced expression of semaphorin 3E is involved in the gastric cancer development.Int J Oncol. 2016 Sep;49(3):887-94. doi: 10.3892/ijo.2016.3593. Epub 2016 Jun 30.
10	Semaphorin 3E expression correlates inversely with Plexin D1 during tumor progression.Am J Pathol. 2008 Dec;173(6):1873-81. doi: 10.2353/ajpath.2008.080136. Epub 2008 Oct 30.
11	Divergent roles of Plexin D1 in cancer.Biochim Biophys Acta Rev Cancer. 2019 Aug;1872(1):103-110. doi: 10.1016/j.bbcan.2019.05.004. Epub 2019 May 30.
12	Semaphorin-3E attenuates intestinal inflammation through the regulation of the communication between splenic CD11C(+) and CD4(+) CD25(-) T-cells.Br J Pharmacol. 2019 May;176(9):1235-1250. doi: 10.1111/bph.14614. Epub 2019 Apr 1.
13	A SEMA3E mutant resistant to cleavage by furins (UNCL-SEMA3E) inhibits choroidal neovascularization.Exp Eye Res. 2016 Dec;153:186-194. doi: 10.1016/j.exer.2016.10.004. Epub 2016 Oct 7.
14	A role for class 3 semaphorins in prostate cancer.Prostate. 2011 May;71(6):649-58. doi: 10.1002/pros.21281. Epub 2010 Oct 14.
15	Semaphorin 3E Deficiency Exacerbates Airway Inflammation, Hyperresponsiveness, and Remodeling in a Mouse Model of Allergic Asthma.J Immunol. 2017 Mar 1;198(5):1805-1814. doi: 10.4049/jimmunol.1601514. Epub 2017 Jan 20.
16	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
17	Peptide vaccine for semaphorin3E ameliorates systemic glucose intolerance in mice with dietary obesity.Sci Rep. 2019 Mar 7;9(1):3858. doi: 10.1038/s41598-019-40325-y.
18	Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in agedrats.Neurobiol Aging. 2018 Oct;70:102-116. doi: 10.1016/j.neurobiolaging.2018.06.003. Epub 2018 Jun 11.
19	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
20	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.
21	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
22	RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
23	Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
24	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.
25	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.
26	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
27	Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
28	Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
29	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.
30	Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
31	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.
32	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.
33	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.