Details of Drug Off-Target (DOT)

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

• DOT Name: Heat shock protein beta-7 (HSPB7)
• Synonyms: HspB7; Cardiovascular heat shock protein; cvHsp
• Gene Name: HSPB7
• Related Disease:
  Advanced cancer
  Arrhythmia
  Cardiomyopathy
  Clear cell renal carcinoma
  Congestive heart failure
  Dilated cardiomyopathy
  Myocardial infarction
  Neoplasm
  Renal cell carcinoma
  Cardiac failure
  Systolic heart failure
• UniProt ID: HSPB7_HUMAN
• Pfam ID: PF00011
• Sequence:
  MSHRTSSTFRAERSFHSSSSSSSSSTSSSASRALPAQDPPMEKALSMFSDDFGSFMRPHS
  EPLAFPARPGGAGNIKTLGDAYEFAVDVRDFSPEDIIVTTSNNHIEVRAEKLAADGTVMN
  TFAHKCQLPEDVDPTSVTSALREDGSLTIRARRHPHTEHVQQTFRTEIKI
• Tissue Specificity: Isoform 1 is highly expressed in adult and fetal heart, skeletal muscle, and at a much lower levels in adipose tissue and in aorta. Undetectable in other tissues. Isoform 2 and isoform 3 are poorly detected in heart.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[1]
Arrhythmia	DISFF2NI	Strong	Genetic Variation	[2]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[3]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[5]
Dilated cardiomyopathy	DISX608J	Strong	Genetic Variation	[6]
Myocardial infarction	DIS655KI	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[4]
Cardiac failure	DISDC067	moderate	Biomarker	[5]
Systolic heart failure	DISSFU1K	Limited	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Heat shock protein beta-7 (HSPB7).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Heat shock protein beta-7 (HSPB7).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Heat shock protein beta-7 (HSPB7).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Heat shock protein beta-7 (HSPB7).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Heat shock protein beta-7 (HSPB7).	[11]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Heat shock protein beta-7 (HSPB7).	[12]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Heat shock protein beta-7 (HSPB7).	[13]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Heat shock protein beta-7 (HSPB7).	[14]
Pantothenic acid	DM091H2	Approved	Pantothenic acid increases the expression of Heat shock protein beta-7 (HSPB7).	[15]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Heat shock protein beta-7 (HSPB7).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heat shock protein beta-7 (HSPB7).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Heat shock protein beta-7 (HSPB7).	[19]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Heat shock protein beta-7 (HSPB7).	[20]

References

• [1] SRARP and HSPB7 are epigenetically regulated gene pairs that function as tumor suppressors and predict clinical outcome in malignancies.Mol Oncol. 2018 May;12(5):724-755. doi: 10.1002/1878-0261.12195. Epub 2018 Apr 16.
• [2] HSPB7 prevents cardiac conduction system defect through maintaining intercalated disc integrity.PLoS Genet. 2017 Aug 21;13(8):e1006984. doi: 10.1371/journal.pgen.1006984. eCollection 2017 Aug.
• [3] Hspb7 is a cardioprotective chaperone facilitating sarcomeric proteostasis.Dev Biol. 2018 Mar 1;435(1):41-55. doi: 10.1016/j.ydbio.2018.01.005. Epub 2018 Jan 10.
• [4] Downregulation of the tumor suppressor HSPB7, involved in the p53 pathway, in renal cell carcinoma by hypermethylation.Int J Oncol. 2014 May;44(5):1490-8. doi: 10.3892/ijo.2014.2314. Epub 2014 Feb 27.
• [5] Dynamic adaptation of myocardial proteome during heart failure development.PLoS One. 2017 Oct 3;12(10):e0185915. doi: 10.1371/journal.pone.0185915. eCollection 2017.
• [6] Association between polymorphisms of the HSPB7 gene and Cheyne-Stokes respiration with central sleep apnea in patients with dilated cardiomyopathy and congestive heart failure.Int J Cardiol. 2016 Oct 15;221:926-31. doi: 10.1016/j.ijcard.2016.07.107. Epub 2016 Jul 9.
• [7] Cardiac signaling genes exhibit unexpected sequence diversity in sporadic cardiomyopathy, revealing HSPB7 polymorphisms associated with disease.J Clin Invest. 2010 Jan;120(1):280-9. doi: 10.1172/JCI39085. Epub 2009 Dec 14.
• [8] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [13] Folate deficiency in normal human fibroblasts leads to altered expression of genes primarily linked to cell signaling, the cytoskeleton and extracellular matrix. J Nutr Biochem. 2007 Aug;18(8):541-52. doi: 10.1016/j.jnutbio.2006.11.002. Epub 2007 Feb 22.
• [14] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [15] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [16] Impact of epigallocatechin gallate on gene expression profiles of human hepatocellular carcinoma cell lines BEL7404/ADM and BEL7402/5-FU. Ai Zheng. 2008 Oct;27(10):1056-64.
• [17] 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.
• [18] 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.
• [19] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [20] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.