Details of Drug Off-Target (DOT)

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

DOT Name	Semaphorin-3B (SEMA3B)
Synonyms	Sema A(V); Semaphorin-V; Sema V
Gene Name	SEMA3B
Related Disease	Adenocarcinoma ( ) Kidney cancer ( ) Squamous cell carcinoma ( ) Adult glioblastoma ( ) Advanced cancer ( ) Autism spectrum disorder ( ) Breast cancer ( ) Breast carcinoma ( ) Cholangiocarcinoma ( ) Endometrial cancer ( ) Endometrial carcinoma ( ) Endometrium neoplasm ( ) Esophageal squamous cell carcinoma ( ) Gastric cancer ( ) Glioblastoma multiforme ( ) Glioma ( ) Hepatocellular carcinoma ( ) Lung carcinoma ( ) Lung neoplasm ( ) Malignant mesothelioma ( ) Mental disorder ( ) Neuroblastoma ( ) Non-small-cell lung cancer ( ) Prostate cancer ( ) Prostate carcinoma ( ) Pulmonary disease ( ) Small-cell lung cancer ( ) Stomach cancer ( ) Carcinoma ( ) Lung cancer ( ) Gallbladder carcinoma ( ) Kennedy disease ( ) Neoplasm ( )
UniProt ID	SEM3B_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00047 ; PF01403
Sequence	MGRAGAAAVIPGLALLWAVGLGSAAPSPPRLRLSFQELQAWHGLQTFSLERTCCYQALLV DEERGRLFVGAENHVASLNLDNISKRAKKLAWPAPVEWREECNWAGKDIGTECMNFVKLL HAYNRTHLLACGTGAFHPTCAFVEVGHRAEEPVLRLDPGRIEDGKGKSPYDPRHRAASVL VGEELYSGVAADLMGRDFTIFRSLGQRPSLRTEPHDSRWLNEPKFVKVFWIPESENPDDD KIYFFFRETAVEAAPALGRLSVSRVGQICRNDVGGQRSLVNKWTTFLKARLVCSVPGVEG DTHFDQLQDVFLLSSRDHRTPLLYAVFSTSSSIFQGSAVCVYSMNDVRRAFLGPFAHKEG PMHQWVSYQGRVPYPRPGMCPSKTFGTFSSTKDFPDDVIQFARNHPLMYNSVLPTGGRPL FLQVGANYTFTQIAADRVAAADGHYDVLFIGTDVGTVLKVISVPKGSRPSAEGLLLEELH VFEDSAAVTSMQISSKRHQLYVASRSAVAQIALHRCAAHGRVCTECCLARDPYCAWDGVA CTRFQPSAKRRFRRQDVRNGDPSTLCSGDSSRPALLEHKVFGVEGSSAFLECEPRSLQAR VEWTFQRAGVTAHTQVLAEERTERTARGLLLRRLRRRDSGVYLCAAVEQGFTQPLRRLSL HVLSATQAERLARAEEAAPAAPPGPKLWYRDFLQLVEPGGGGSANSLRMCRPQPALQSLP LESRRKGRNRRTHAPEPRAERGPRSATHW
Function	Inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons.
Tissue Specificity	Expressed abundantly but differentially in a variety of neural and nonneural tissues.
KEGG Pathway	Axon guidance (hsa04360 )

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adenocarcinoma	DIS3IHTY	Definitive	Posttranslational Modification	[1]
Kidney cancer	DISBIPKM	Definitive	Genetic Variation	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Posttranslational Modification	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cholangiocarcinoma	DIS71F6X	Strong	Posttranslational Modification	[6]
Endometrial cancer	DISW0LMR	Strong	Altered Expression	[3]
Endometrial carcinoma	DISXR5CY	Strong	Altered Expression	[3]
Endometrium neoplasm	DIS6OS2L	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[9]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[12]
Lung neoplasm	DISVARNB	Strong	Genetic Variation	[13]
Malignant mesothelioma	DISTHJGH	Strong	Altered Expression	[14]
Mental disorder	DIS3J5R8	Strong	Genetic Variation	[15]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[18]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[18]
Pulmonary disease	DIS6060I	Strong	Posttranslational Modification	[19]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[1]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[9]
Carcinoma	DISH9F1N	moderate	Biomarker	[20]
Lung cancer	DISCM4YA	moderate	Genetic Variation	[12]
Gallbladder carcinoma	DISD6ACL	Limited	Posttranslational Modification	[21]
Kennedy disease	DISXZVM1	Limited	Genetic Variation	[22]
Neoplasm	DISZKGEW	Limited	Biomarker	[8]
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⏷ Show the Full List of 33 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mifepristone	DMGZQEF	Approved	Semaphorin-3B (SEMA3B) increases the response to substance of Mifepristone.	[7]
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3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Semaphorin-3B (SEMA3B).	[23]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Semaphorin-3B (SEMA3B).	[35]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Semaphorin-3B (SEMA3B).	[39]
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19 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 Semaphorin-3B (SEMA3B).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Semaphorin-3B (SEMA3B).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Semaphorin-3B (SEMA3B).	[26]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Semaphorin-3B (SEMA3B).	[27]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Semaphorin-3B (SEMA3B).	[28]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Semaphorin-3B (SEMA3B).	[29]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Semaphorin-3B (SEMA3B).	[30]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Semaphorin-3B (SEMA3B).	[31]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Semaphorin-3B (SEMA3B).	[32]
Selenium	DM25CGV	Approved	Selenium increases the expression of Semaphorin-3B (SEMA3B).	[33]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Semaphorin-3B (SEMA3B).	[7]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Semaphorin-3B (SEMA3B).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Semaphorin-3B (SEMA3B).	[37]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Semaphorin-3B (SEMA3B).	[38]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Semaphorin-3B (SEMA3B).	[30]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Semaphorin-3B (SEMA3B).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Semaphorin-3B (SEMA3B).	[40]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Semaphorin-3B (SEMA3B).	[41]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Semaphorin-3B (SEMA3B).	[36]
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⏷ Show the Full List of 19 Drug(s)

References

1	Tumor Suppressor Function of the SEMA3B Gene in Human Lung and Renal Cancers.PLoS One. 2015 May 11;10(5):e0123369. doi: 10.1371/journal.pone.0123369. eCollection 2015.
2	MiR-374b targets GATA3 to promote progression and development of glioblastoma via regulating SEMA3B.Neoplasma. 2019 Jul 23;66(4):543-554. doi: 10.4149/neo_2018_180830N659. Epub 2019 Mar 7.
3	Expression of Semaphorin 3B (SEMA3B) in Various Grades of Endometrial Cancer.Med Sci Monit. 2019 Jun 20;25:4569-4574. doi: 10.12659/MSM.916762.
4	Teaching Literacy Skills to French Minimally Verbal School-Aged Children with Autism Spectrum Disorders with the Serious Game SEMA-TIC: An Exploratory Study.Front Psychol. 2017 Sep 5;8:1523. doi: 10.3389/fpsyg.2017.01523. eCollection 2017.
5	GATA3 targets semaphorin 3B in mammary epithelial cells to suppress breast cancer progression and metastasis.Oncogene. 2017 Oct 5;36(40):5567-5575. doi: 10.1038/onc.2017.165. Epub 2017 Jun 5.
6	Allele loss and epigenetic inactivation of 3p21.3 in malignant liver tumors.Int J Cancer. 2005 Jul 10;115(5):684-9. doi: 10.1002/ijc.20944.
7	Progesterone and 1,25-dihydroxyvitamin D? inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F. Mol Cancer Res. 2011 Nov;9(11):1479-92. doi: 10.1158/1541-7786.MCR-11-0213. Epub 2011 Sep 20.
8	Promoter hypermethylation-mediated downregulation of tumor suppressor gene SEMA3B and lncRNA SEMA3B-AS1 correlates with progression and prognosis of esophageal squamous cell carcinoma.Clin Exp Metastasis. 2019 Jun;36(3):225-241. doi: 10.1007/s10585-019-09964-3. Epub 2019 Mar 27.
9	Analysis of SEMA3B methylation and expression patterns in gastric cancer tissue and cell lines.Oncol Rep. 2014 Mar;31(3):1211-8. doi: 10.3892/or.2014.2972. Epub 2014 Jan 9.
10	Mechanism of SEMA3B gene silencing and clinical significance in glioma.Genet Mol Res. 2016 Mar 18;15(1). doi: 10.4238/gmr.15017664.
11	Doxorubicin-induced epithelial-mesenchymal transition through SEMA 4A in hepatocellular carcinoma.Biochem Biophys Res Commun. 2016 Oct 28;479(4):610-614. doi: 10.1016/j.bbrc.2016.09.167. Epub 2016 Sep 30.
12	Impaired ligand-dependent MET activation caused by an extracellular SEMA domain missense mutation in lung cancer.Cancer Sci. 2019 Oct;110(10):3340-3349. doi: 10.1111/cas.14142. Epub 2019 Aug 13.
13	The race associated allele of Semaphorin 3B (SEMA3B) T415I and its role in lung cancer in African-Americans and Latino-Americans.Carcinogenesis. 2005 Aug;26(8):1446-9. doi: 10.1093/carcin/bgi098. Epub 2005 Apr 14.
14	Frequent deletion of 3p21.1 region carrying semaphorin 3G and aberrant expression of the genes participating in semaphorin signaling in the epithelioid type of malignant mesothelioma cells.Int J Oncol. 2011 Dec;39(6):1365-74. doi: 10.3892/ijo.2011.1158. Epub 2011 Aug 12.
15	"When I Stop My Medication, Everything Goes Wrong": Content Analysis of Interviews with Adolescent Patients Treated with Psychotropic Medication.J Child Adolesc Psychopharmacol. 2018 Nov;28(9):655-662. doi: 10.1089/cap.2018.0072. Epub 2018 Aug 27.
16	High-resolution analysis of 3p deletion in neuroblastoma and differential methylation of the SEMA3B tumor suppressor gene. Cancer Genet Cytogenet. 2007 Apr 15;174(2):100-10. doi: 10.1016/j.cancergencyto.2006.11.017.
17	Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer.Cancer Lett. 2005 Jul 8;225(1):131-9. doi: 10.1016/j.canlet.2004.10.041. Epub 2004 Dec 22.
18	Semaphorin 3B and 3F single nucleotide polymorphisms are associated with prostate cancer risk and poor prognosis.J Urol. 2009 Oct;182(4):1614-20. doi: 10.1016/j.juro.2009.06.016. Epub 2009 Aug 15.
19	Aberrant promoter methylation of p16(INK4a), RARB2 and SEMA3B in bronchial aspirates from patients with suspected lung cancer.Int J Cancer. 2005 Sep 20;116(5):720-5. doi: 10.1002/ijc.21090.
20	MiR-6872 host gene SEMA3B and its antisense lncRNA SEMA3B-AS1 function synergistically to suppress gastric cardia adenocarcinoma progression.Gastric Cancer. 2019 Jul;22(4):705-722. doi: 10.1007/s10120-019-00924-0. Epub 2019 Jan 17.
21	Frequent epigenetic inactivation of chromosome 3p candidate tumor suppressor genes in gallbladder carcinoma.Cancer Lett. 2007 May 18;250(1):100-6. doi: 10.1016/j.canlet.2006.09.019. Epub 2006 Nov 7.
22	Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.Mol Oncol. 2018 Apr;12(4):495-513. doi: 10.1002/1878-0261.12177. Epub 2018 Mar 1.
23	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.
24	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.
25	High-resolution analysis of 3p deletion in neuroblastoma and differential methylation of the SEMA3B tumor suppressor gene. Cancer Genet Cytogenet. 2007 Apr 15;174(2):100-10. doi: 10.1016/j.cancergencyto.2006.11.017.
26	Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
27	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
28	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.
29	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
30	Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
31	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.
32	Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
33	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
34	Progesterone and 1,25-dihydroxyvitamin D? inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F. Mol Cancer Res. 2011 Nov;9(11):1479-92. doi: 10.1158/1541-7786.MCR-11-0213. Epub 2011 Sep 20.
35	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.
36	Transcriptional changes common to human cocaine, cannabis and phencyclidine abuse. PLoS One. 2006 Dec 27;1(1):e114. doi: 10.1371/journal.pone.0000114.
37	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.
38	A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
39	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.
40	Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
41	Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
42	Progesterone and 1,25-dihydroxyvitamin D? inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F. Mol Cancer Res. 2011 Nov;9(11):1479-92. doi: 10.1158/1541-7786.MCR-11-0213. Epub 2011 Sep 20.