Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRE2H4G)

• DOT Name: Fatty acid-binding protein, brain (FABP7)
• Synonyms: Brain lipid-binding protein; BLBP; Brain-type fatty acid-binding protein; B-FABP; Fatty acid-binding protein 7; Mammary-derived growth inhibitor related
• Gene Name: FABP7
• Related Disease:
  Anaplastic astrocytoma
  Bipolar disorder
  Acute liver failure
  Adult glioblastoma
  Advanced cancer
  Alzheimer disease
  Astrocytoma
  Autism
  Autism spectrum disorder
  B-cell lymphoma
  Brain cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Depression
  Epilepsy
  Glioblastoma multiforme
  Glioma
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
  Malignant peripheral nerve sheath tumor
  Melanoma
  Metastatic malignant neoplasm
  Multiple sclerosis
  Neoplasm
  Nervous system inflammation
  Psoriasis
  Renal cell carcinoma
  Schizophrenia
  Triple negative breast cancer
  Carcinoma
  Hirschsprung disease
  Invasive breast carcinoma
  Aplasia cutis congenita
  Clear cell renal carcinoma
  Corpus callosum, agenesis of
  Cutaneous melanoma
  Fetal growth restriction
  Malignant glioma
  Nervous system disease
  Neuroblastoma
• UniProt ID: FABP7_HUMAN
• PDB ID: 1FDQ; 1FE3; 1JJX; 5URA; 6L9O; 7E25
• Pfam ID: PF00061
• Sequence:
  MVEAFCATWKLTNSQNFDEYMKALGVGFATRQVGNVTKPTVIISQEGDKVVIRTLSTFKN
  TEISFQLGEEFDETTADDRNCKSVVSLDGDKLVHIQKWDGKETNFVREIKDGKMVMTLTF
  GDVVAVRHYEKA
• Function: B-FABP could be involved in the transport of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development. It is required for the establishment of the radial glial fiber system in developing brain, a system that is necessary for the migration of immature neurons to establish cortical layers.
• Tissue Specificity: Expressed in brain and other neural tissues.
• KEGG Pathway: PPAR sig.ling pathway (hsa03320)
• Reactome Pathway:
  NOTCH3 Intracellular Domain Regulates Transcription (R-HSA-9013508)
  Triglyceride catabolism (R-HSA-163560)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anaplastic astrocytoma	DISSBE0K	Definitive	Biomarker	[1]
Bipolar disorder	DISAM7J2	Definitive	Biomarker	[2]
Acute liver failure	DIS5EZKX	Strong	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Astrocytoma	DISL3V18	Strong	Altered Expression	[6]
Autism	DISV4V1Z	Strong	Biomarker	[7]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[8]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[9]
Brain cancer	DISBKFB7	Strong	Biomarker	[10]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[10]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[10]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Biomarker	[12]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[12]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[12]
Depression	DIS3XJ69	Strong	Biomarker	[13]
Epilepsy	DISBB28L	Strong	Biomarker	[14]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[15]
Glioma	DIS5RPEH	Strong	Altered Expression	[5]
Her2-receptor negative breast cancer	DISS605N	Strong	Biomarker	[10]
HER2/NEU overexpressing breast cancer	DISYKID5	Strong	Biomarker	[10]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[16]
Melanoma	DIS1RRCY	Strong	Altered Expression	[17]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[18]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[12]
Nervous system inflammation	DISB3X5A	Strong	Biomarker	[19]
Psoriasis	DIS59VMN	Strong	Altered Expression	[20]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[21]
Schizophrenia	DISSRV2N	Strong	Biomarker	[22]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	moderate	Altered Expression	[21]
Hirschsprung disease	DISUUSM1	moderate	Biomarker	[23]
Invasive breast carcinoma	DISANYTW	Disputed	Altered Expression	[24]
Aplasia cutis congenita	DISMDAYM	Limited	Altered Expression	[25]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[26]
Corpus callosum, agenesis of	DISO9P40	Limited	Altered Expression	[25]
Cutaneous melanoma	DIS3MMH9	Limited	Altered Expression	[27]
Fetal growth restriction	DIS5WEJ5	Limited	Altered Expression	[28]
Malignant glioma	DISFXKOV	Limited	Biomarker	[29]
Nervous system disease	DISJ7GGT	Limited	Altered Expression	[30]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Fatty acid-binding protein, brain (FABP7) decreases the response to substance of Eicosapentaenoic acid/docosa-hexaenoic acid.	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fatty acid-binding protein, brain (FABP7).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fatty acid-binding protein, brain (FABP7).	[32]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Fatty acid-binding protein, brain (FABP7).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Fatty acid-binding protein, brain (FABP7).	[34]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Fatty acid-binding protein, brain (FABP7).	[35]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fatty acid-binding protein, brain (FABP7).	[36]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Fatty acid-binding protein, brain (FABP7).	[37]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Fatty acid-binding protein, brain (FABP7).	[38]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Fatty acid-binding protein, brain (FABP7).	[39]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Fatty acid-binding protein, brain (FABP7).	[40]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Fatty acid-binding protein, brain (FABP7).	[41]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Fatty acid-binding protein, brain (FABP7).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fatty acid-binding protein, brain (FABP7).	[44]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Fatty acid-binding protein, brain (FABP7).	[45]

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 increases the methylation of Fatty acid-binding protein, brain (FABP7).	[43]

References

• [1] Fatty acid binding protein 7 as a marker of glioma stem cells.Pathol Int. 2013 Nov;63(11):546-53. doi: 10.1111/pin.12109.
• [2] Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder.Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):484-493. doi: 10.1002/ajmg.b.31004.
• [3] The association between FABP7 serum levels with survival and neurological complications in acetaminophen-induced acute liver failure: a nested case-control study.Ann Intensive Care. 2017 Oct 5;7(1):99. doi: 10.1186/s13613-017-0323-0.
• [4] Metabolic role of fatty acid binding protein 7 in mediating triple-negative breast cancer cell death via PPAR- signaling.J Lipid Res. 2019 Nov;60(11):1807-1817. doi: 10.1194/jlr.M092379. Epub 2019 Sep 4.
• [5] FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation.Mol Neurobiol. 2019 Aug;56(8):5763-5779. doi: 10.1007/s12035-019-1489-2. Epub 2019 Jan 24.
• [6] BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions.Brain Behav Immun. 2011 Nov;25(8):1554-68. doi: 10.1016/j.bbi.2011.05.003. Epub 2011 May 17.
• [7] Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association studies in autism and schizophrenia in Japanese subjects.J Hum Genet. 2010 Feb;55(2):127-30. doi: 10.1038/jhg.2009.133. Epub 2010 Jan 8.
• [8] Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies.Hum Mol Genet. 2014 Dec 15;23(24):6495-511. doi: 10.1093/hmg/ddu369. Epub 2014 Jul 15.
• [9] Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma.Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):E3534-43. doi: 10.1073/pnas.1405507111. Epub 2014 Aug 11.
• [10] FABP7 is a key metabolic regulator in HER2+ breast cancer brain metastasis.Oncogene. 2019 Sep;38(37):6445-6460. doi: 10.1038/s41388-019-0893-4. Epub 2019 Jul 19.
• [11] A fatty acid-binding protein 7/RXR pathway enhances survival and proliferation in triple-negative breast cancer. J Pathol. 2012 Nov;228(3):310-21. doi: 10.1002/path.4001. Epub 2012 Apr 18.
• [12] FABP7 promotes cell proliferation and survival in colon cancer through MEK/ERK signaling pathway.Biomed Pharmacother. 2018 Dec;108:119-129. doi: 10.1016/j.biopha.2018.08.038. Epub 2018 Sep 13.
• [13] The nuclear receptor REV-ERB regulates Fabp7 and modulates adult hippocampal neurogenesis.PLoS One. 2014 Jun 16;9(6):e99883. doi: 10.1371/journal.pone.0099883. eCollection 2014.
• [14] Developmental lineage of cell types in cortical dysplasia with balloon cells.Brain. 2007 Sep;130(Pt 9):2267-76. doi: 10.1093/brain/awm175.
• [15] A positive feedback loop involving nuclear factor IB and calpain 1 suppresses glioblastoma cell migration.J Biol Chem. 2019 Aug 23;294(34):12638-12654. doi: 10.1074/jbc.RA119.008291. Epub 2019 Jul 1.
• [16] Brain lipid binding protein in axon-Schwann cell interactions and peripheral nerve tumorigenesis.Mol Cell Biol. 2003 Mar;23(6):2213-24. doi: 10.1128/MCB.23.6.2213-2224.2003.
• [17] Melanoma-associated cancer-testis antigen 16 (CT16) regulates the expression of apoptotic and antiapoptotic genes and promotes cell survival. PLoS One. 2012;7(9):e45382.
• [18] The fatty acid binding protein 7 (FABP7) is involved in proliferation and invasion of melanoma cells.BMC Cancer. 2008 Sep 30;8:276. doi: 10.1186/1471-2407-8-276.
• [19] The role of fatty acid binding protein 7 in spinal cord astrocytes in a mouse model of experimental autoimmune encephalomyelitis.Neuroscience. 2019 Jun 15;409:120-129. doi: 10.1016/j.neuroscience.2019.03.050. Epub 2019 Apr 30.
• [20] Reduced stratum corneum acylceramides in autosomal recessive congenital ichthyosis with a NIPAL4 mutation.J Dermatol Sci. 2020 Jan;97(1):50-56. doi: 10.1016/j.jdermsci.2019.12.001. Epub 2019 Dec 4.
• [21] Functional analysis of fatty acid binding protein 7 and its effect on fatty acid of renal cell carcinoma cell lines.BMC Cancer. 2017 Mar 14;17(1):192. doi: 10.1186/s12885-017-3184-x.
• [22] Evaluation of the role of fatty acid-binding protein 7 in controlling schizophrenia-relevant phenotypes using newly established knockout mice.Schizophr Res. 2020 Mar;217:52-59. doi: 10.1016/j.schres.2019.02.002. Epub 2019 Feb 11.
• [23] Differential expressions of BMPR1, ACTN4 and FABP7 in Hirschsprung disease.Int J Clin Exp Pathol. 2014 Apr 15;7(5):2312-8. eCollection 2014.
• [24] The proteins FABP7 and OATP2 are associated with the basal phenotype and patient outcome in human breast cancer.Breast Cancer Res Treat. 2010 May;121(1):41-51. doi: 10.1007/s10549-009-0450-x. Epub 2009 Jul 10.
• [25] The Prognostic Significance of Notch1 and Fatty Acid Binding Protein 7 (FABP7) Expression in Resected Tracheobronchial Adenoid Cystic Carcinoma: A Multicenter Retrospective Study.Cancer Res Treat. 2018 Oct;50(4):1064-1073. doi: 10.4143/crt.2017.337. Epub 2017 Nov 15.
• [26] Fatty acid binding protein 7 may be a marker and therapeutic targets in clear cell renal cell carcinoma.BMC Cancer. 2018 Nov 15;18(1):1114. doi: 10.1186/s12885-018-5060-8.
• [27] Aberrant fatty acid-binding protein-7 gene expression in cutaneous malignant melanoma.J Invest Dermatol. 2010 Jan;130(1):221-9. doi: 10.1038/jid.2009.195.
• [28] Antenatal taurine supplementation in fetal rats with growth restriction improves neural stem cell proliferation by inhibiting the activities of Rho family factors.J Matern Fetal Neonatal Med. 2018 Jun;31(11):1454-1461. doi: 10.1080/14767058.2017.1319353. Epub 2017 May 5.
• [29] Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma.Prog Lipid Res. 2013 Oct;52(4):562-70. doi: 10.1016/j.plipres.2013.08.004. Epub 2013 Aug 24.
• [30] Overexpression of FABP7 in Down syndrome fetal brains is associated with PKNOX1 gene-dosage imbalance.Nucleic Acids Res. 2003 Jun 1;31(11):2769-77. doi: 10.1093/nar/gkg396.
• [31] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [32] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [33] 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.
• [34] 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.
• [35] 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.
• [36] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [37] Evaluation of developmental toxicity using undifferentiated human embryonic stem cells. J Appl Toxicol. 2015 Feb;35(2):205-18.
• [38] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [39] 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.
• [40] Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro. Toxicology. 2023 Mar 15;487:153461. doi: 10.1016/j.tox.2023.153461. Epub 2023 Feb 16.
• [41] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [42] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
• [43] 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.
• [44] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [45] 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.
• [46] A fatty acid-binding protein 7/RXR pathway enhances survival and proliferation in triple-negative breast cancer. J Pathol. 2012 Nov;228(3):310-21. doi: 10.1002/path.4001. Epub 2012 Apr 18.