Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTUB5KS)

• DOT Name: Protein BRICK1 (BRK1)
• Synonyms: BRK1
• Gene Name: BRK1
• Related Disease:
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Non-small-cell lung cancer
  Von hippel-lindau disease
  Neoplasm
  Neuroblastoma
• UniProt ID: BRK1_HUMAN
• PDB ID: 3P8C; 4N78; 7USC; 7USD; 7USE
• Sequence:
  MAGQEDPVQREIHQDWANREYIEIITSSIKKIADFLNSFDMSCRSRLATLNEKLTALERR
  IEYIEARVTKGETLT
• Function: Involved in regulation of actin and microtubule organization. Part of a WAVE complex that activates the Arp2/3 complex. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes.
• KEGG Pathway:
  Regulation of actin cytoskeleton (hsa04810)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  VEGFA-VEGFR2 Pathway (R-HSA-4420097)
  RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213)
  RAC1 GTPase cycle (R-HSA-9013149)
  RAC2 GTPase cycle (R-HSA-9013404)
  RAC3 GTPase cycle (R-HSA-9013423)
  FCGR3A-mediated phagocytosis (R-HSA-9664422)
  Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[2]
Von hippel-lindau disease	DIS6ZFQQ	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein BRICK1 (BRK1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein BRICK1 (BRK1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein BRICK1 (BRK1).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein BRICK1 (BRK1).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein BRICK1 (BRK1).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein BRICK1 (BRK1).	[9]

References

• [1] Metastatic potential of lung squamous cell carcinoma associated with HSPC300 through its interaction with WAVE2.Lung Cancer. 2009 Sep;65(3):299-305. doi: 10.1016/j.lungcan.2009.06.001. Epub 2009 Jul 2.
• [2] Sp1 transcriptionally regulates BRK1 expression in non-small cell lung cancer cells.Gene. 2014 Jun 1;542(2):134-40. doi: 10.1016/j.gene.2014.03.043. Epub 2014 Mar 25.
• [3] Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation.Cancer Res. 2010 Nov 15;70(22):9349-59. doi: 10.1158/0008-5472.CAN-09-4491. Epub 2010 Sep 22.
• [4] Novel genes FAM134C, C3orf10 and ENOX1 are regulated by NRF-1 and differentially regulate neurite outgrowth in neuroblastoma cells and hippocampal neurons.Gene. 2013 Oct 15;529(1):7-15. doi: 10.1016/j.gene.2013.08.006. Epub 2013 Aug 9.
• [5] 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.
• [6] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [7] 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.
• [8] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.