Details of Drug Off-Target (DOT)

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

• DOT Name: HSPB1-associated protein 1 (HSPBAP1)
• Synonyms: 27 kDa heat shock protein-associated protein 1; Protein associated with small stress protein 1
• Gene Name: HSPBAP1
• Related Disease:
  Cystic fibrosis
  Epilepsy
  Prostate cancer
  Prostate carcinoma
• UniProt ID: HBAP1_HUMAN
• Pfam ID: PF13621
• Sequence:
  MAAGSEATTPVIVAAGAGGEEGEHVKPFKPEKAKEIIMSLQQPAIFCNMVFDWPARHWNA
  KYLSQVLHGKQIRFRMGMKSMSTVPQFETTCNYVEATLEEFLTWNCDQSSISGPFRDYDH
  SKFWAYADYKYFVSLFEDKTDLFQDVKWSDFGFPGRNGQESTLWIGSLGAHTPCHLDSYG
  CNLVFQVQGRKRWHLFPPEDTPFLYPTRIPYEESSVFSKINVVNPDLKRFPQFRKAQRHA
  VTLSPGQVLFVPRHWWHYVESIDPVTVSINSWIELEEDHLARVEEAITRMLVCALKTAEN
  PQNTRAWLNPTEVEETSHAVNCCYLNAAVSAFFDRCRTSEVVEIQALRTDGEHMKKEELN
  VCNHMEVGQTGSQNLTTGTDKPEAASPFGPDLVPVAQRSEEPPSERGGIFGSDGKDFVDK
  DGEHFGKLHCAKRQQIMSNSENAIEEQIASNTTTTPQTFISTDDLLDCLVNPQVTRIVAQ
  LLIQGRSL
• Function: May play a role in cellular stress response.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[1]
Epilepsy	DISBB28L	Strong	Altered Expression	[2]
Prostate cancer	DISF190Y	Limited	Biomarker	[3]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[3]

15 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 HSPB1-associated protein 1 (HSPBAP1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of HSPB1-associated protein 1 (HSPBAP1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of HSPB1-associated protein 1 (HSPBAP1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of HSPB1-associated protein 1 (HSPBAP1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of HSPB1-associated protein 1 (HSPBAP1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of HSPB1-associated protein 1 (HSPBAP1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of HSPB1-associated protein 1 (HSPBAP1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of HSPB1-associated protein 1 (HSPBAP1).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of HSPB1-associated protein 1 (HSPBAP1).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of HSPB1-associated protein 1 (HSPBAP1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of HSPB1-associated protein 1 (HSPBAP1).	[10]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of HSPB1-associated protein 1 (HSPBAP1).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of HSPB1-associated protein 1 (HSPBAP1).	[14]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of HSPB1-associated protein 1 (HSPBAP1).	[16]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of HSPB1-associated protein 1 (HSPBAP1).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of HSPB1-associated protein 1 (HSPBAP1).	[15]

References

• [1] Dual Transcriptomics of Host-Pathogen Interaction of Cystic Fibrosis Isolate Pseudomonas aeruginosa PASS1 With Zebrafish.Front Cell Infect Microbiol. 2018 Nov 22;8:406. doi: 10.3389/fcimb.2018.00406. eCollection 2018.
• [2] HSPBAP1 is found extensively in the anterior temporal neocortex of patients with intractable epilepsy.Synapse. 2007 Sep;61(9):741-7. doi: 10.1002/syn.20417.
• [3] Androgen receptor-interacting protein HSPBAP1 facilitates growth of prostate cancer cells in androgen-deficient conditions.Int J Cancer. 2015 Jun 1;136(11):2535-45. doi: 10.1002/ijc.29303. Epub 2014 Nov 20.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] 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.
• [13] Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.
• [14] 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.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.