Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE67YM5)

• DOT Name: Heat shock protein beta-3 (HSPB3)
• Synonyms: HspB3; Heat shock 17 kDa protein; HSP 17; Protein 3
• Gene Name: HSPB3
• Related Disease:
  Distal hereditary motor neuropathy type 2
  Neuronopathy, distal hereditary motor, type 2C
• UniProt ID: HSPB3_HUMAN
• PDB ID: 6F2R
• Pfam ID: PF00011
• Sequence:
  MAKIILRHLIEIPVRYQEEFEARGLEDCRLDHALYALPGPTIVDLRKTRAAQSPPVDSAA
  ETPPREGKSHFQILLDVVQFLPEDIIIQTFEGWLLIKAQHGTRMDEHGFISRSFTRQYKL
  PDGVEIKDLSAVLCHDGILVVEVKDPVGTK
• Function: Inhibitor of actin polymerization.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Distal hereditary motor neuropathy type 2	DIS162V1	Supportive	Autosomal dominant	[1]
Neuronopathy, distal hereditary motor, type 2C	DISEMTVB	Limited	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Heat shock protein beta-3 (HSPB3).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Heat shock protein beta-3 (HSPB3).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Heat shock protein beta-3 (HSPB3).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Heat shock protein beta-3 (HSPB3).	[5]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of Heat shock protein beta-3 (HSPB3).	[6]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Heat shock protein beta-3 (HSPB3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heat shock protein beta-3 (HSPB3).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Heat shock protein beta-3 (HSPB3).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Heat shock protein beta-3 (HSPB3).	[11]

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 protein beta-3 (HSPB3).	[8]

References

• [1] Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach. Neurology. 2010 Feb 9;74(6):502-6. doi: 10.1212/WNL.0b013e3181cef84a.
• [2] 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.
• [3] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [4] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
• [7] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [8] 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.
• [9] 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.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] 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.