Details of Drug Off-Target (DOT)

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

• DOT Name: Heat shock factor-binding protein 1 (HSBP1)
• Synonyms: Nasopharyngeal carcinoma-associated antigen 13; NPC-A-13
• Gene Name: HSBP1
• Related Disease:
  Advanced cancer
  Breast neoplasm
  Chronic obstructive pulmonary disease
• UniProt ID: HSBP1_HUMAN
• PDB ID: 3CI9
• Pfam ID: PF06825
• Sequence:
  MAETDPKTVQDLTSVVQTLLQQMQDKFQTMSDQIIGRIDDMSSRIDDLEKNIADLMTQAG
  VEELESENKIPATQKS
• Function: Negative regulator of the heat shock response. Negatively affects HSF1 DNA-binding activity. May have a role in the suppression of the activation of the stress response during the aging process.
• Reactome Pathway:
  Attenuation phase (R-HSA-3371568)
  HSF1-dependent transactivation (R-HSA-3371571)
  HSF1 activation (R-HSA-3371511)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]

9 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 Heat shock factor-binding protein 1 (HSBP1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Heat shock factor-binding protein 1 (HSBP1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Heat shock factor-binding protein 1 (HSBP1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Heat shock factor-binding protein 1 (HSBP1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Heat shock factor-binding protein 1 (HSBP1).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Heat shock factor-binding protein 1 (HSBP1).	[8]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Heat shock factor-binding protein 1 (HSBP1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heat shock factor-binding protein 1 (HSBP1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Heat shock factor-binding protein 1 (HSBP1).	[12]

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 Heat shock factor-binding protein 1 (HSBP1).	[10]

References

• [1] The trimeric coiled-coil HSBP1 protein promotes WASH complex assembly at centrosomes.EMBO J. 2018 Jul 2;37(13):e97706. doi: 10.15252/embj.201797706. Epub 2018 May 29.
• [2] A genome-wide analysis of the response to inhaled 2-agonists in chronic obstructive pulmonary disease.Pharmacogenomics J. 2016 Aug;16(4):326-35. doi: 10.1038/tpj.2015.65. Epub 2015 Oct 27.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [10] 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.
• [11] 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.
• [12] 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.