Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAZ5OP8)

• DOT Name: Endophilin-B1 (SH3GLB1)
• Synonyms: Bax-interacting factor 1; Bif-1; SH3 domain-containing GRB2-like protein B1
• Gene Name: SH3GLB1
• Related Disease:
  Lung adenocarcinoma
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Carcinoma
  Gastric cancer
  Glioma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Stomach cancer
  Stroke
  Hepatocellular carcinoma
  Adenocarcinoma
  Colorectal adenocarcinoma
• UniProt ID: SHLB1_HUMAN
• PDB ID: 6UP6; 6UPN
• Pfam ID: PF03114 ; PF14604
• Sequence:
  MNIMDFNVKKLAADAGTFLSRAVQFTEEKLGQAEKTELDAHLENLLSKAECTKIWTEKIM
  KQTEVLLQPNPNARIEEFVYEKLDRKAPSRINNPELLGQYMIDAGTEFGPGTAYGNALIK
  CGETQKRIGTADRELIQTSALNFLTPLRNFIEGDYKTIAKERKLLQNKRLDLDAAKTRLK
  KAKAAETRNSSEQELRITQSEFDRQAEITRLLLEGISSTHAHHLRCLNDFVEAQMTYYAQ
  CYQYMLDLQKQLGSFPSNYLSNNNQTSVTPVPSVLPNAIGSSAMASTSGLVITSPSNLSD
  LKECSGSRKARVLYDYDAANSTELSLLADEVITVFSVVGMDSDWLMGERGNQKGKVPITY
  LELLN
• Function: May be required for normal outer mitochondrial membrane dynamics. Required for coatomer-mediated retrograde transport in certain cells. May recruit other proteins to membranes with high curvature. May promote membrane fusion. Involved in activation of caspase-dependent apoptosis by promoting BAX/BAK1 activation. Isoform 1 acts proapoptotic in fibroblasts. Involved in caspase-independent apoptosis during nutrition starvation and involved in the regulation of autophagy. Activates lipid kinase activity of PIK3C3 during autophagy probably by associating with the PI3K complex II (PI3KC3-C2). Associated with PI3KC3-C2 during autophagy may regulate the trafficking of ATG9A from the Golgi complex to the peripheral cytoplasm for the formation of autophagosomes by inducing Golgi membrane tubulation and fragmentation. Involved in regulation of degradative endocytic trafficking and cytokinesis, probably in the context of PI3KC3-C2. Isoform 2 acts antiapoptotic in neuronal cells; involved in maintenance of mitochondrial morphology and promotes neuronal viability.
• Tissue Specificity: Highly expressed in heart, skeletal muscle, kidney and placenta. Detected at lower levels in brain, colon, thymus, spleen, liver, small intestine, lung and peripheral blood leukocytes.
• KEGG Pathway:
  Autophagy - animal (hsa04140)
  Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung adenocarcinoma	DISD51WR	Definitive	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[4]
Glioma	DIS5RPEH	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[7]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[7]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[8]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[4]
Stroke	DISX6UHX	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[6]
Adenocarcinoma	DIS3IHTY	Disputed	Altered Expression	[9]
Colorectal adenocarcinoma	DISPQOUB	Limited	Altered Expression	[9]

22 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 Endophilin-B1 (SH3GLB1).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Endophilin-B1 (SH3GLB1).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Endophilin-B1 (SH3GLB1).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Endophilin-B1 (SH3GLB1).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Endophilin-B1 (SH3GLB1).	[14]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Endophilin-B1 (SH3GLB1).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endophilin-B1 (SH3GLB1).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Endophilin-B1 (SH3GLB1).	[17]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Endophilin-B1 (SH3GLB1).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Endophilin-B1 (SH3GLB1).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Endophilin-B1 (SH3GLB1).	[19]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Endophilin-B1 (SH3GLB1).	[20]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Endophilin-B1 (SH3GLB1).	[19]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Endophilin-B1 (SH3GLB1).	[21]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Endophilin-B1 (SH3GLB1).	[22]
Atazanavir	DMSYRBX	Approved	Atazanavir increases the expression of Endophilin-B1 (SH3GLB1).	[22]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Endophilin-B1 (SH3GLB1).	[23]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Endophilin-B1 (SH3GLB1).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Endophilin-B1 (SH3GLB1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endophilin-B1 (SH3GLB1).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Endophilin-B1 (SH3GLB1).	[27]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Endophilin-B1 (SH3GLB1).	[28]

References

• [1] Molecular profiling of mouse lung tumors: association with tumor progression, lung development, and human lung adenocarcinomas.Oncogene. 2004 Feb 5;23(5):1166-76. doi: 10.1038/sj.onc.1207234.
• [2] Neuronal susceptibility to beta-amyloid toxicity and ischemic injury involves histone deacetylase-2 regulation of endophilin-B1.Brain Pathol. 2019 Mar;29(2):164-175. doi: 10.1111/bpa.12647. Epub 2018 Oct 5.
• [3] Bif-1 suppresses breast cancer cell migration by promoting EGFR endocytic degradation.Cancer Biol Ther. 2012 Aug;13(10):956-66. doi: 10.4161/cbt.20951. Epub 2012 Aug 1.
• [4] Decreased expression of tumour suppressor Bax-interacting factor-1 (Bif-1), a Bax activator, in gastric carcinomas.Pathology. 2006 Aug;38(4):312-5. doi: 10.1080/00313020600820880.
• [5] Autophagy-related gene expression is an independent prognostic indicator of glioma.Oncotarget. 2017 May 9;8(37):60987-61000. doi: 10.18632/oncotarget.17719. eCollection 2017 Sep 22.
• [6] Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity.Clin Exp Metastasis. 2017 Jan;34(1):11-23. doi: 10.1007/s10585-016-9825-7. Epub 2016 Oct 11.
• [7] Roles of Alternative RNA Splicing of the Bif-1 Gene by SRRM4 During the Development of Treatment-induced Neuroendocrine Prostate Cancer.EBioMedicine. 2018 May;31:267-275. doi: 10.1016/j.ebiom.2018.05.002. Epub 2018 May 16.
• [8] Bax-interacting factor-1 expression in prostate cancer.Clin Genitourin Cancer. 2008 Sep;6(2):117-21. doi: 10.3816/CGC.2008.n.018.
• [9] Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma.Cancer. 2008 Nov 15;113(10):2665-70. doi: 10.1002/cncr.23892.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] 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.
• [12] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [13] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [14] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [15] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [16] 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.
• [17] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [18] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [19] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [20] 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.
• [21] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [22] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [23] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [24] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [25] 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.
• [26] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [27] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [28] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.