Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ71SK9)

• DOT Name: Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1)
• Synonyms: BAI1-associated protein 2-like protein 1; Insulin receptor tyrosine kinase substrate
• Gene Name: BAIAP2L1
• Related Disease:
  Advanced cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Carcinoma
  Lung cancer
  Neoplasm
  Rheumatoid arthritis
• UniProt ID: BI2L1_HUMAN
• PDB ID: 2KXC; 2LNH
• Pfam ID: PF08397 ; PF14604
• Sequence:
  MSRGPEEVNRLTESTYRNVMEQFNPGLRNLINLGKNYEKAVNAMILAGKAYYDGVAKIGE
  IATGSPVSTELGHVLIEISSTHKKLNESLDENFKKFHKEIIHELEKKIELDVKYMNATLK
  RYQTEHKNKLESLEKSQAELKKIRRKSQGSRNALKYEHKEIEYVETVTSRQSEIQKFIAD
  GCKEALLEEKRRFCFLVDKHCGFANHIHYYHLQSAELLNSKLPRWQETCVDAIKVPEKIM
  NMIEEIKTPASTPVSGTPQASPMIERSNVVRKDYDTLSKCSPKMPPAPSGRAYTSPLIDM
  FNNPATAAPNSQRVNNSTGTSEDPSLQRSVSVATGLNMMKKQKVKTIFPHTAGSNKTLLS
  FAQGDVITLLIPEEKDGWLYGEHDVSKARGWFPSSYTKLLEENETEAVTVPTPSPTPVRS
  ISTVNLSENSSVVIPPPDYLECLSMGAAADRRADSARTTSTFKAPASKPETAAPNDANGT
  AKPPFLSGENPFATVKLRPTVTNDRSAPIIR
• Function: May function as adapter protein. Involved in the formation of clusters of actin bundles. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection.
• KEGG Pathway: Pathogenic Escherichia coli infection (hsa05130)
• Reactome Pathway:
  RAC2 GTPase cycle (R-HSA-9013404)
  RAC3 GTPase cycle (R-HSA-9013423)
  RHOF GTPase cycle (R-HSA-9035034)
  RAC1 GTPase cycle (R-HSA-9013149)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Carcinoma	DISH9F1N	Limited	Genetic Variation	[3]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[3]
Neoplasm	DISZKGEW	Limited	Genetic Variation	[4]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Streptozocin	DMOF7AT	Approved	Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1) increases the Hyperinsulinism ADR of Streptozocin.	[25]

5 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 Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[21]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[21]

17 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 Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[10]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[17]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[23]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1).	[24]

References

• [1] BAI1-Associated Protein 2-Like 1 (BAIAP2L1) Is a Potential Biomarker in Ovarian Cancer.PLoS One. 2015 Jul 29;10(7):e0133081. doi: 10.1371/journal.pone.0133081. eCollection 2015.
• [2] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [3] A novel somatic FGFR3 mutation in primary lung cancer.Oncol Rep. 2014 Mar;31(3):1219-24. doi: 10.3892/or.2014.2984. Epub 2014 Jan 20.
• [4] The landscape of fusion transcripts in spitzoid melanoma and biologically indeterminate spitzoid tumors by RNA sequencing.Mod Pathol. 2016 Apr;29(4):359-69. doi: 10.1038/modpathol.2016.37. Epub 2016 Feb 19.
• [5] Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity.Genes Immun. 2007 Sep;8(6):480-91. doi: 10.1038/sj.gene.6364400. Epub 2007 Jun 14.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] 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.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [17] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [18] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [19] 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.
• [20] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [21] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [22] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [23] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [24] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [25] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.