Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF7BB9S)

• DOT Name: Endophilin-B2 (SH3GLB2)
• Synonyms: SH3 domain-containing GRB2-like protein B2
• Gene Name: SH3GLB2
• Related Disease:
  Influenza
  Metastatic malignant neoplasm
  Prostate adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
• UniProt ID: SHLB2_HUMAN
• Pfam ID: PF03114 ; PF14604
• Sequence:
  MDFNMKKLASDAGIFFTRAVQFTEEKFGQAEKTELDAHFENLLARADSTKNWTEKILRQT
  EVLLQPNPSARVEEFLYEKLDRKVPSRVTNGELLAQYMADAASELGPTTPYGKTLIKVAE
  AEKQLGAAERDFIHTASISFLTPLRNFLEGDWKTISKERRLLQNRRLDLDACKARLKKAK
  AAEAKATTVPDFQETRPRNYILSASASALWNDEVDKAEQELRVAQTEFDRQAEVTRLLLE
  GISSTHVNHLRCLHEFVKSQTTYYAQCYRHMLDLQKQLGRFPGTFVGTTEPASPPLSSTS
  PTTAAATMPVVPSVASLAPPGEASLCLEEVAPPASGTRKARVLYDYEAADSSELALLADE
  LITVYSLPGMDPDWLIGERGNKKGKVPVTYLELLS
• Tissue Specificity: Detected in skeletal muscle, adipocyte, brain, lung, colon and mammary gland.
• KEGG Pathway: Endocytosis (hsa04144)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Influenza	DIS3PNU3	Strong	Biomarker	[1]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[2]
Prostate adenocarcinoma	DISBZYU8	Strong	Biomarker	[2]
Prostate cancer	DISF190Y	Strong	Altered Expression	[2]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[2]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Endophilin-B2 (SH3GLB2) affects the response to substance of Methotrexate.	[13]

9 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 Endophilin-B2 (SH3GLB2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Endophilin-B2 (SH3GLB2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Endophilin-B2 (SH3GLB2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Endophilin-B2 (SH3GLB2).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Endophilin-B2 (SH3GLB2).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Endophilin-B2 (SH3GLB2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Endophilin-B2 (SH3GLB2).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Endophilin-B2 (SH3GLB2).	[11]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Endophilin-B2 (SH3GLB2).	[12]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Endophilin-B2 (SH3GLB2).	[9]

References

• [1] SH3GLB2/endophilin B2 regulates lung homeostasis and recovery from severe influenza A virus infection.Sci Rep. 2017 Aug 4;7(1):7262. doi: 10.1038/s41598-017-07724-5.
• [2] SPAS-1 (stimulator of prostatic adenocarcinoma-specific T cells)/SH3GLB2: A prostate tumor antigen identified by CTLA-4 blockade.Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3509-14. doi: 10.1073/pnas.0712269105. Epub 2008 Feb 26.
• [3] 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.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [12] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [13] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.