Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS01646)

DOT Name	Heat shock protein beta-2 (HSPB2)
Synonyms	HspB2; DMPK-binding protein; MKBP
Gene Name	HSPB2
Related Disease	Uveal Melanoma ( ) Advanced cancer ( ) Alzheimer disease ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Bladder cancer ( ) Bone osteosarcoma ( ) Breast cancer ( ) Breast carcinoma ( ) Breast neoplasm ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Castration-resistant prostate carcinoma ( ) Cerebral infarction ( ) Charcot marie tooth disease ( ) Charcot-Marie-Tooth disease axonal type 2F ( ) Colon carcinoma ( ) Colorectal carcinoma ( ) Coronary atherosclerosis ( ) Esophageal squamous cell carcinoma ( ) Glioma ( ) Head-neck squamous cell carcinoma ( ) Hepatocellular carcinoma ( ) Liver cancer ( ) Lung cancer ( ) Lung carcinoma ( ) Metastatic malignant neoplasm ( ) Myocardial infarction ( ) Neuroblastoma ( ) Osteosarcoma ( ) Pancreatic cancer ( ) Pneumonitis ( ) Prostate cancer ( ) Prostate carcinoma ( ) Prostate neoplasm ( ) Squamous cell carcinoma ( ) Stomach cancer ( ) Type-1/2 diabetes ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Cardiovascular disease ( ) Colon cancer ( ) Glioblastoma multiforme ( ) Adult glioblastoma ( ) Acute myelogenous leukaemia ( ) Alexander disease ( ) Gastric cancer ( ) Melanoma ( )
UniProt ID	HSPB2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	6F2R
Pfam ID	PF00525 ; PF00011
Sequence	MSGRSVPHAHPATAEYEFANPSRLGEQRFGEGLLPEEILTPTLYHGYYVRPRAAPAGEGS RAGASELRLSEGKFQAFLDVSHFTPDEVTVRTVDNLLEVSARHPQRLDRHGFVSREFCRT YVLPADVDPWRVRAALSHDGILNLEAPRGGRHLDTEVNEVYISLLPAPPDPEEEEEAAIV EP
Function	May regulate the kinase DMPK.
Tissue Specificity	Expressed preferentially in skeletal muscle and heart but not in the lens.
KEGG Pathway	Proteoglycans in cancer (hsa05205 )

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Uveal Melanoma	DISA7ZGL	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[4]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[4]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[9]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[10]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[11]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[12]
Charcot-Marie-Tooth disease axonal type 2F	DIS4U2DX	Strong	Genetic Variation	[13]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[14]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[15]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[16]
Glioma	DIS5RPEH	Strong	Altered Expression	[17]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[18]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[19]
Liver cancer	DISDE4BI	Strong	Biomarker	[9]
Lung cancer	DISCM4YA	Strong	Biomarker	[20]
Lung carcinoma	DISTR26C	Strong	Biomarker	[20]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[21]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[22]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[23]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Pancreatic cancer	DISJC981	Strong	Biomarker	[24]
Pneumonitis	DIS88E0K	Strong	Biomarker	[25]
Prostate cancer	DISF190Y	Strong	Altered Expression	[26]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[26]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[27]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[28]
Stomach cancer	DISKIJSX	Strong	Biomarker	[29]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[30]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[5]
Cardiovascular disease	DIS2IQDX	moderate	Altered Expression	[31]
Colon cancer	DISVC52G	moderate	Biomarker	[14]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[32]
Adult glioblastoma	DISVP4LU	Disputed	Biomarker	[32]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[33]
Alexander disease	DISDL1IO	Limited	Biomarker	[34]
Gastric cancer	DISXGOUK	Limited	Biomarker	[29]
Melanoma	DIS1RRCY	Limited	Biomarker	[35]
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⏷ Show the Full List of 47 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Heat shock protein beta-2 (HSPB2) decreases the response to substance of Doxorubicin.	[45]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Heat shock protein beta-2 (HSPB2).	[36]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Heat shock protein beta-2 (HSPB2).	[37]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Heat shock protein beta-2 (HSPB2).	[38]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Heat shock protein beta-2 (HSPB2).	[39]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Heat shock protein beta-2 (HSPB2).	[41]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Heat shock protein beta-2 (HSPB2).	[42]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Heat shock protein beta-2 (HSPB2).	[43]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Heat shock protein beta-2 (HSPB2).	[44]
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⏷ Show the Full List of 8 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the phosphorylation of Heat shock protein beta-2 (HSPB2).	[40]
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References

1	A multiplex immunoassay of serum biomarkers for the detection of uveal melanoma.Clin Proteomics. 2019 Mar 5;16:10. doi: 10.1186/s12014-019-9230-8. eCollection 2019.
2	Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma.World J Clin Cases. 2019 Feb 6;7(3):260-269. doi: 10.12998/wjcc.v7.i3.260.
3	Novel compound VB-037 inhibits A aggregation and promotes neurite outgrowth through enhancement of HSP27 and reduction of P38 and JNK-mediated inflammation in cell models for Alzheimer's disease.Neurochem Int. 2019 May;125:175-186. doi: 10.1016/j.neuint.2019.01.021. Epub 2019 Jan 29.
4	Protective effect of HSP27 in atherosclerosis and coronary heart disease by inhibiting reactive oxygen species.J Cell Biochem. 2019 Mar;120(3):2859-2868. doi: 10.1002/jcb.26575. Epub 2018 Dec 3.
5	Clinical, prognostic, and therapeutic significance of heat shock protein 27 in bladder cancer.Oncotarget. 2018 Jan 8;9(8):7961-7974. doi: 10.18632/oncotarget.24091. eCollection 2018 Jan 30.
6	Analysis of HSP27 and the Autophagy Marker LC3B(+) Puncta Following Preoperative Chemotherapy Identifies High-Risk Osteosarcoma Patients.Mol Cancer Ther. 2018 Jun;17(6):1315-1323. doi: 10.1158/1535-7163.MCT-17-0901. Epub 2018 Mar 28.
7	Simultaneous quantification of Cyt c interactions with HSP27 and Bcl-xL using molecularly imprinted polymers (MIPs) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics.J Proteomics. 2019 Feb 10;192:188-195. doi: 10.1016/j.jprot.2018.09.001. Epub 2018 Sep 17.
8	Phosphorylation of Ser78 of Hsp27 correlated with HER-2/neu status and lymph node positivity in breast cancer.Mol Cancer. 2007 Aug 14;6:52. doi: 10.1186/1476-4598-6-52.
9	SUMOylation of HSP27 by small ubiquitin-like modifier 2/3 promotes proliferation and invasion of hepatocellular carcinoma cells.Cancer Biol Ther. 2017 Aug 3;18(8):552-559. doi: 10.1080/15384047.2017.1345382. Epub 2017 Jun 30.
10	Correction: Targeting Hsp27/eIF4E interaction with phenazine compound: a promising alternative for castration-resistant prostate cancer treatment.Oncotarget. 2018 Jun 19;9(47):28797. doi: 10.18632/oncotarget.25683. eCollection 2018 Jun 19.
11	Pentose phosphate pathway activation via HSP27 phosphorylation by ATM kinase: A putative endogenous antioxidant defense mechanism during cerebral ischemia-reperfusion.Brain Res. 2018 May 15;1687:82-94. doi: 10.1016/j.brainres.2018.03.001. Epub 2018 Mar 3.
12	Charcot-Marie-Tooth 2F (Hsp27 mutations): A review.Neurobiol Dis. 2019 Oct;130:104505. doi: 10.1016/j.nbd.2019.104505. Epub 2019 Jun 15.
13	Decreased ceramide underlies mitochondrial dysfunction in Charcot-Marie-Tooth 2F.FASEB J. 2018 Mar;32(3):1716-1728. doi: 10.1096/fj.201701067R. Epub 2018 Jan 3.
14	MiR-214 sensitizes human colon cancer cells to 5-FU by targeting Hsp27.Cell Mol Biol Lett. 2019 Mar 14;24:22. doi: 10.1186/s11658-019-0143-3. eCollection 2019.
15	Heat shock protein 27 knockdown using nucleotidebased therapies enhances sensitivity to 5-FU chemotherapy in SW480 human colon cancer cells.Oncol Rep. 2018 Mar;39(3):1119-1124. doi: 10.3892/or.2018.6180. Epub 2018 Jan 3.
16	Expression of Heat Shock Protein-27 (Hsp27) and P38MAPK in Esophageal Squamous Cell Carcinoma.Med Sci Monit. 2017 Nov 3;23:5246-5253. doi: 10.12659/msm.904912.
17	Rosmarinic acid and siRNA combined therapy represses Hsp27 (HSPB1) expression and induces apoptosis in human glioma cells.Cell Stress Chaperones. 2018 Sep;23(5):885-896. doi: 10.1007/s12192-018-0896-z. Epub 2018 Apr 7.
18	p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells.J Clin Invest. 2010 Apr;120(4):1165-77. doi: 10.1172/JCI40582. Epub 2010 Mar 15.
19	The clinicopathological and prognostic value of HSP27 in hepatocellular carcinoma: a systematic review and meta-analysis.Onco Targets Ther. 2018 Mar 7;11:1293-1303. doi: 10.2147/OTT.S154227. eCollection 2018.
20	Induction of HSP27 and HSP70 by constitutive overexpression of Redd1 confers resistance of lung cancer cells to ionizing radiation.Oncol Rep. 2019 May;41(5):3119-3126. doi: 10.3892/or.2019.7036. Epub 2019 Feb 28.
21	HSP27, ALDH6A1 and Prohibitin Act as a Trio-biomarker to Predict Survival in Late Metastatic Prostate Cancer.Anticancer Res. 2018 Nov;38(11):6551-6560. doi: 10.21873/anticanres.13021.
22	Characterization of heat shock protein 27 in extracellular vesicles: a potential anti-inflammatory therapy.FASEB J. 2019 Feb;33(2):1617-1630. doi: 10.1096/fj.201800987R. Epub 2018 Sep 6.
23	Treatment of human neuroblastoma cell line SH-SY5Y with HSP27 siRNA tagged-exosomes decreased differentiation rate into mature neurons.J Cell Physiol. 2019 Nov;234(11):21005-21013. doi: 10.1002/jcp.28704. Epub 2019 Apr 22.
24	Molecular chaperone HspB2 inhibited pancreatic cancer cell proliferation via activating p53 downstream gene RPRM, BAI1, and TSAP6.J Cell Biochem. 2020 Mar;121(3):2318-2329. doi: 10.1002/jcb.29455. Epub 2019 Nov 6.
25	HSP27 inhibitor attenuates radiation-induced pulmonary inflammation.Sci Rep. 2018 Mar 8;8(1):4189. doi: 10.1038/s41598-018-22635-9.
26	Hsp-27 and NF-B pathway is associated with AR/AR-V7 expression in prostate cancer cells.Gene. 2019 May 20;697:138-143. doi: 10.1016/j.gene.2019.02.055. Epub 2019 Feb 23.
27	Molecular chaperone Hsp27 regulates the Hippo tumor suppressor pathway in cancer.Sci Rep. 2016 Aug 24;6:31842. doi: 10.1038/srep31842.
28	Overexpression of heat shock protein 27 in squamous cell carcinoma of the uterine cervix: a proteomic analysis using archival formalin-fixed, paraffin-embedded tissues.Hum Pathol. 2009 Jan;40(1):41-9. doi: 10.1016/j.humpath.2008.06.010. Epub 2008 Aug 27.
29	Clinicopathological significance of HSP27 in gastric cancer: a meta-analysis.Onco Targets Ther. 2017 Sep 13;10:4543-4551. doi: 10.2147/OTT.S146590. eCollection 2017.
30	Circulating levels of Hsp27 in microvascular complications of diabetes: Prospects as a biomarker of diabetic nephropathy.J Diabetes Complications. 2018 Feb;32(2):221-225. doi: 10.1016/j.jdiacomp.2017.10.004. Epub 2017 Oct 16.
31	4-Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe(-/-) mice.FASEB J. 2019 Jul;33(7):8406-8422. doi: 10.1096/fj.201802293RR. Epub 2019 Apr 9.
32	Delineation of crosstalk between HSP27 and MMP-2/MMP-9: A synergistic therapeutic avenue for glioblastoma management.Biochim Biophys Acta Gen Subj. 2019 Jul;1863(7):1196-1209. doi: 10.1016/j.bbagen.2019.04.015. Epub 2019 Apr 25.
33	Hsp27: a novel therapeutic target for pediatric M4/M5 acute myeloid leukemia.Oncol Rep. 2013 Apr;29(4):1459-66. doi: 10.3892/or.2013.2274. Epub 2013 Feb 5.
34	Synemin is expressed in reactive astrocytes and Rosenthal fibers in Alexander disease.APMIS. 2014 Jan;122(1):76-80. doi: 10.1111/apm.12088. Epub 2013 Apr 18.
35	Heat-shock protein 27 (HSP27, HSPB1) is synthetic lethal to cells with oncogenic activation of MET, EGFR and BRAF.Mol Oncol. 2017 Jun;11(6):599-611. doi: 10.1002/1878-0261.12042. Epub 2017 May 8.
36	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
37	Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
38	Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
39	Selenium is critical for cancer-signaling gene expression but not cell proliferation in human colon Caco-2 cells. Biofactors. 2007;31(3-4):155-64. doi: 10.1002/biof.5520310302.
40	Molecular basis for the induction of an angiogenesis inhibitor, thrombospondin-1, by 5-fluorouracil. Cancer Res. 2008 Sep 1;68(17):7035-41. doi: 10.1158/0008-5472.CAN-07-6496.
41	Role of HSP27 and reduced glutathione in modulating malathion-induced apoptosis of human peripheral blood mononuclear cells: ameliorating effect of N-acetylcysteine and curcumin. Toxicol In Vitro. 2009 Oct;23(7):1319-25. doi: 10.1016/j.tiv.2009.07.016. Epub 2009 Jul 14.
42	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.
43	Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
44	Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors. Toxicology. 2010 Jan 31;268(1-2):19-24. doi: 10.1016/j.tox.2009.11.013. Epub 2009 Nov 14.
45	Nuclear proteomics with XRCC3 knockdown to reveal the development of doxorubicin-resistant uterine cancer. Toxicol Sci. 2014 Jun;139(2):396-406. doi: 10.1093/toxsci/kfu051. Epub 2014 Mar 27.