Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCJ2EZY)

DOT Name High mobility group protein B3 (HMGB3)
Synonyms High mobility group protein 2a; HMG-2a; High mobility group protein 4; HMG-4
Gene Name HMGB3
Related Disease
Small-cell lung cancer ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Digestive system neoplasm ( )
Epithelial ovarian cancer ( )
Hepatocellular carcinoma ( )
Liver cirrhosis ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Microphthalmia, isolated, with coloboma ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Prostate cancer ( )
Prostate carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Colorectal carcinoma ( )
Gastric cancer ( )
leukaemia ( )
Leukemia ( )
Non-small-cell lung cancer ( )
Stomach cancer ( )
Adult glioblastoma ( )
Advanced cancer ( )
Carcinoma of liver and intrahepatic biliary tract ( )
Fetal growth restriction ( )
Glioblastoma multiforme ( )
Intellectual disability ( )
Liver cancer ( )
X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome ( )
UniProt ID
HMGB3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2EQZ; 2YQI
Pfam ID
PF00505 ; PF09011
Sequence
MAKGDPKKPKGKMSAYAFFVQTCREEHKKKNPEVPVNFAEFSKKCSERWKTMSGKEKSKF
DEMAKADKVRYDREMKDYGPAKGGKKKKDPNAPKRPPSGFFLFCSEFRPKIKSTNPGISI
GDVAKKLGEMWNNLNDSEKQPYITKAAKLKEKYEKDVADYKSKGKFDGAKGPAKVARKKV
EEEDEEEEEEEEEEEEEEDE
Function
Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. Associates with chromatin and binds DNA with a preference for non-canonical DNA structures such as single-stranded DNA. Can bend DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters. Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor. Negatively regulates B-cell and myeloid cell differentiation. In hematopoietic stem cells may regulate the balance between self-renewal and differentiation. Involved in negative regulation of canonical Wnt signaling.
Tissue Specificity Expressed predominantly in placenta.

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Small-cell lung cancer DISK3LZD Definitive Genetic Variation [1]
Bladder cancer DISUHNM0 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Biomarker [3]
Breast carcinoma DIS2UE88 Strong Biomarker [3]
Cervical cancer DISFSHPF Strong Biomarker [4]
Cervical carcinoma DIST4S00 Strong Biomarker [4]
Digestive system neoplasm DISPOJCT Strong Altered Expression [5]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [6]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [7]
Liver cirrhosis DIS4G1GX Strong Biomarker [8]
Lung adenocarcinoma DISD51WR Strong Biomarker [9]
Lung cancer DISCM4YA Strong Biomarker [10]
Lung carcinoma DISTR26C Strong Biomarker [10]
Microphthalmia, isolated, with coloboma DISLSEUJ Strong Genetic Variation [11]
Neoplasm DISZKGEW Strong Biomarker [12]
Ovarian cancer DISZJHAP Strong Biomarker [6]
Ovarian neoplasm DISEAFTY Strong Biomarker [6]
Prostate cancer DISF190Y Strong Altered Expression [13]
Prostate carcinoma DISMJPLE Strong Altered Expression [13]
Urinary bladder cancer DISDV4T7 Strong Biomarker [2]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [2]
Colorectal carcinoma DIS5PYL0 moderate Altered Expression [14]
Gastric cancer DISXGOUK moderate Biomarker [5]
leukaemia DISS7D1V moderate Biomarker [15]
Leukemia DISNAKFL moderate Biomarker [15]
Non-small-cell lung cancer DIS5Y6R9 moderate Biomarker [16]
Stomach cancer DISKIJSX moderate Biomarker [5]
Adult glioblastoma DISVP4LU Limited Biomarker [17]
Advanced cancer DISAT1Z9 Limited Altered Expression [7]
Carcinoma of liver and intrahepatic biliary tract DIS8WA0W Limited Biomarker [7]
Fetal growth restriction DIS5WEJ5 Limited Altered Expression [18]
Glioblastoma multiforme DISK8246 Limited Biomarker [17]
Intellectual disability DISMBNXP Limited Biomarker [19]
Liver cancer DISDE4BI Limited Biomarker [7]
X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome DISZY8A1 Limited Unknown [20]
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⏷ Show the Full List of 35 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
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 High mobility group protein B3 (HMGB3). [21]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of High mobility group protein B3 (HMGB3). [22]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of High mobility group protein B3 (HMGB3). [23]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of High mobility group protein B3 (HMGB3). [24]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of High mobility group protein B3 (HMGB3). [25]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of High mobility group protein B3 (HMGB3). [26]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of High mobility group protein B3 (HMGB3). [27]
Menadione DMSJDTY Approved Menadione affects the expression of High mobility group protein B3 (HMGB3). [28]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of High mobility group protein B3 (HMGB3). [29]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of High mobility group protein B3 (HMGB3). [30]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of High mobility group protein B3 (HMGB3). [31]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of High mobility group protein B3 (HMGB3). [32]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of High mobility group protein B3 (HMGB3). [33]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of High mobility group protein B3 (HMGB3). [34]
geraniol DMS3CBD Investigative geraniol decreases the expression of High mobility group protein B3 (HMGB3). [35]
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⏷ Show the Full List of 15 Drug(s)

References

1 Multigene real-time PCR detection of circulating tumor cells in peripheral blood of lung cancer patients.Anticancer Res. 2006 Mar-Apr;26(2B):1567-75.
2 Downregulation of microRNA-532-5p promotes the proliferation and invasion of bladder cancer cells through promotion of HMGB3/Wnt/-catenin signaling.Chem Biol Interact. 2019 Feb 25;300:73-81. doi: 10.1016/j.cbi.2019.01.015. Epub 2019 Jan 11.
3 HMGB3 small interfere RNA suppresses mammosphere formation of MDA-MB-231 cells by down-regulating expression of HIF1.Eur Rev Med Pharmacol Sci. 2019 Nov;23(21):9506-9516. doi: 10.26355/eurrev_201911_19445.
4 MicroRNA-758 inhibits cervical cancer cell proliferation and metastasis by targeting HMGB3 through the WNT/-catenin signaling pathway.Oncol Lett. 2019 Aug;18(2):1786-1792. doi: 10.3892/ol.2019.10470. Epub 2019 Jun 12.
5 Bioinformatics analysis of the prognosis and biological significance of HMGB1, HMGB2, and HMGB3 in gastric cancer.J Cell Physiol. 2020 Apr;235(4):3438-3446. doi: 10.1002/jcp.29233. Epub 2019 Oct 16.
6 Targeting the High-Mobility Group Box 3 Protein Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin.Cancer Res. 2019 Jul 1;79(13):3185-3191. doi: 10.1158/0008-5472.CAN-19-0542. Epub 2019 May 6.
7 Abnormal expression of HMGB-3 is significantly associated with malignant transformation of hepatocytes.World J Gastroenterol. 2018 Aug 28;24(32):3650-3662. doi: 10.3748/wjg.v24.i32.3650.
8 High mobility group box 3 as an emerging biomarker in diagnosis and prognosis of hepatocellular carcinoma.Cancer Manag Res. 2018 Nov 20;10:5979-5989. doi: 10.2147/CMAR.S181742. eCollection 2018.
9 Secreted phosphoprotein 1 upstream invasive network construction and analysis of lung adenocarcinoma compared with human normal adjacent tissues by integrative biocomputation.Cell Biochem Biophys. 2010 Apr;56(2-3):59-71. doi: 10.1007/s12013-009-9071-6.
10 Screening of tumor-associated antigens based on Oncomine database and evaluation of diagnostic value of autoantibodies in lung cancer.Clin Immunol. 2020 Jan;210:108262. doi: 10.1016/j.clim.2019.108262. Epub 2019 Oct 17.
11 Identification of an HMGB3 frameshift mutation in a family with an X-linked colobomatous microphthalmia syndrome using whole-genome and X-exome sequencing.JAMA Ophthalmol. 2014 Oct;132(10):1215-20. doi: 10.1001/jamaophthalmol.2014.1731.
12 HMGB3 silence inhibits breast cancer cell proliferation and tumor growth by interacting with hypoxia-inducible factor 1.Cancer Manag Res. 2019 May 31;11:5075-5089. doi: 10.2147/CMAR.S204357. eCollection 2019.
13 Regulation of HMGB3 by antitumor miR-205-5p inhibits cancer cell aggressiveness and is involved in prostate cancer pathogenesis.J Hum Genet. 2018 Feb;63(2):195-205. doi: 10.1038/s10038-017-0371-1. Epub 2017 Dec 1.
14 Ginkgo biloba extract 761 enhances 5-fluorouracil chemosensitivity in colorectal cancer cells through regulation of high mobility group-box 3 expression.Am J Transl Res. 2018 Jun 15;10(6):1773-1783. eCollection 2018.
15 Upregulation of miR-513b inhibits cell proliferation, migration, and promotes apoptosis by targeting high mobility group-box 3 protein in gastric cancer.Tumour Biol. 2014 Nov;35(11):11081-9. doi: 10.1007/s13277-014-2405-z. Epub 2014 Aug 6.
16 Knockdown of high mobility group box 3 impairs cell viability and colony formation but increases apoptosis in A549 human non-small cell lung cancer cells.Oncol Lett. 2019 Mar;17(3):2937-2945. doi: 10.3892/ol.2019.9927. Epub 2019 Jan 14.
17 HMGB3 promotes the proliferation and metastasis of glioblastoma and is negatively regulated by miR-200b-3p and miR-200c-3p.Cell Biochem Funct. 2018 Oct;36(7):357-365. doi: 10.1002/cbf.3355. Epub 2018 Sep 19.
18 Down-regulated expressed protein HMGB3 inhibits proliferation and migration, promotes apoptosis in the placentas of fetal growth restriction.Int J Biochem Cell Biol. 2019 Feb;107:69-76. doi: 10.1016/j.biocel.2018.11.007. Epub 2018 Dec 10.
19 X-linked colobomatous microphthalmos and other congenital anomalies. A disorder resembling Lenz's dysmorphogenetic syndrome.Am J Ophthalmol. 1971 May;71(5):1128-33. doi: 10.1016/0002-9394(71)90588-5.
20 Hmgb3 deficiency deregulates proliferation and differentiation of common lymphoid and myeloid progenitors. Blood. 2005 Jan 15;105(2):627-34. doi: 10.1182/blood-2004-07-2551. Epub 2004 Sep 9.
21 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
22 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
23 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.
24 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
25 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
26 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.
27 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
28 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.
29 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
30 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
31 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
32 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.
33 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.
34 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
35 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.