Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLVZ13T)

• DOT Name: Thymosin beta-10 (TMSB10)
• Gene Name: TMSB10
• Related Disease:
  Neuroblastoma
  Allergic contact dermatitis
  Arteriosclerosis
  Atherosclerosis
  Bipolar disorder
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Carcinoma of esophagus
  Cholangiocarcinoma
  Clear cell renal carcinoma
  Congenital contractural arachnodactyly
  Cutaneous melanoma
  Lung neoplasm
  Melanoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Renal cell carcinoma
  Schizophrenia
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  X-linked Opitz G/BBB syndrome
  Bladder cancer
  Pancreatic cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adenocarcinoma
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
• UniProt ID: TYB10_HUMAN
• Pfam ID: PF01290
• Sequence: MADKPDMGEIASFDKAKLKKTETQEKNTLPTKETIEQEKRSEIS
• Function: Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.

Molecular Interaction Atlas (MIA) of This DOT

33 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[1]
Allergic contact dermatitis	DISFFVF9	Strong	Biomarker	[2]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[3]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[3]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[5]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[5]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[5]
Carcinoma	DISH9F1N	Strong	Altered Expression	[6]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[7]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[8]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[9]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[8]
Cutaneous melanoma	DIS3MMH9	Strong	Biomarker	[10]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[11]
Melanoma	DIS1RRCY	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[12]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[13]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[9]
Schizophrenia	DISSRV2N	Strong	Biomarker	[4]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[14]
Thyroid gland papillary carcinoma	DIS48YMM	Strong	Altered Expression	[15]
X-linked Opitz G/BBB syndrome	DISQ14EC	Strong	Biomarker	[16]
Bladder cancer	DISUHNM0	moderate	Altered Expression	[17]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[18]
Urinary bladder cancer	DISDV4T7	moderate	Altered Expression	[17]
Urinary bladder neoplasm	DIS7HACE	moderate	Altered Expression	[17]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[6]
Epithelial ovarian cancer	DIS56MH2	Limited	Altered Expression	[13]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[12]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Genetic Variation	[6]

1 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 Thymosin beta-10 (TMSB10).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Thymosin beta-10 (TMSB10).	[20]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Thymosin beta-10 (TMSB10).	[21]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Thymosin beta-10 (TMSB10).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Thymosin beta-10 (TMSB10).	[23]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Thymosin beta-10 (TMSB10).	[24]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Thymosin beta-10 (TMSB10).	[25]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Thymosin beta-10 (TMSB10).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thymosin beta-10 (TMSB10).	[27]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Thymosin beta-10 (TMSB10).	[28]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Thymosin beta-10 (TMSB10).	[29]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Thymosin beta-10 (TMSB10).	[30]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Thymosin beta-10 (TMSB10).	[31]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Thymosin beta-10 (TMSB10).	[32]
Raltitrexed	DMT9K8G	Approved	Raltitrexed increases the expression of Thymosin beta-10 (TMSB10).	[32]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Thymosin beta-10 (TMSB10).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Thymosin beta-10 (TMSB10).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Thymosin beta-10 (TMSB10).	[35]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Thymosin beta-10 (TMSB10).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Thymosin beta-10 (TMSB10).	[37]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Thymosin beta-10 (TMSB10).	[38]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Thymosin beta-10 (TMSB10).	[39]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Thymosin beta-10 (TMSB10).	[40]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Thymosin beta-10 (TMSB10).	[41]

References

• [1] Retinoids and a retinoic acid receptor differentially modulate thymosin beta 10 gene expression in transfected neuroblastoma cells.Cell Mol Neurobiol. 1992 Feb;12(1):45-58. doi: 10.1007/BF00711638.
• [2] Gene expression time course in the human skin during elicitation of allergic contact dermatitis.J Invest Dermatol. 2007 Nov;127(11):2585-95. doi: 10.1038/sj.jid.5700902. Epub 2007 Jun 28.
• [3] Differential expression of thymosin beta-10 by early passage and senescent vascular endothelium is modulated by VPF/VEGF: evidence for senescent endothelial cells in vivo at sites of atherosclerosis.FASEB J. 2001 Feb;15(2):458-66. doi: 10.1096/fj.00-0051com.
• [4] Reduced myelin basic protein and actin-related gene expression in visual cortex in schizophrenia.PLoS One. 2012;7(6):e38211. doi: 10.1371/journal.pone.0038211. Epub 2012 Jun 1.
• [5] Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer.Breast Cancer Res. 2017 Feb 8;19(1):15. doi: 10.1186/s13058-016-0785-2.
• [6] Hypomethylation of the thymosin (10) gene is not associated with its overexpression in non-small cell lung cancer.Mol Cells. 2011 Oct;32(4):343-8. doi: 10.1007/s10059-011-0073-z. Epub 2011 Oct 17.
• [7] Thymosin beta-10 gene overexpression is a general event in human carcinogenesis.Am J Pathol. 1999 Sep;155(3):799-804. doi: 10.1016/s0002-9440(10)65178-4.
• [8] Suppression of thymosin 10 increases cell migration and metastasis of cholangiocarcinoma.BMC Cancer. 2013 Sep 23;13:430. doi: 10.1186/1471-2407-13-430.
• [9] Amplification-independent overexpression of thymosin beta-10 mRNA in human renal cell carcinoma.Ren Fail. 1994;16(2):243-54. doi: 10.3109/08860229409044864.
• [10] Thymosin beta-10 expression in melanoma cell lines and melanocytic lesions: a new progression marker for human cutaneous melanoma.Int J Cancer. 1993 Jan 21;53(2):278-84. doi: 10.1002/ijc.2910530218.
• [11] Expression of thymosin beta10 and its role in non-small cell lung cancer.Hum Pathol. 2009 Jan;40(1):117-24. doi: 10.1016/j.humpath.2008.06.023. Epub 2008 Sep 11.
• [12] Thymosin 10 is overexpressed and associated with unfavorable prognosis in hepatocellular carcinoma.Biosci Rep. 2019 Mar 15;39(3):BSR20182355. doi: 10.1042/BSR20182355. Print 2019 Mar 29.
• [13] Thymosin 10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.PLoS One. 2012;7(5):e35399. doi: 10.1371/journal.pone.0035399. Epub 2012 May 18.
• [14] Thymosin beta-10 gene expression as a possible tool in diagnosis of thyroid neoplasias.Oncol Rep. 2004 Aug;12(2):239-43.
• [15] Thymosin beta 10 correlates with lymph node metastases of papillary thyroid carcinoma.J Surg Res. 2014 Dec;192(2):487-93. doi: 10.1016/j.jss.2014.05.066. Epub 2014 May 27.
• [16] Mig12, a novel Opitz syndrome gene product partner, is expressed in the embryonic ventral midline and co-operates with Mid1 to bundle and stabilize microtubules.BMC Cell Biol. 2004 Feb 29;5:9. doi: 10.1186/1471-2121-5-9.
• [17] Overexpression of thymosin 10 correlates with disease progression and poor prognosis in bladder cancer.Exp Ther Med. 2019 Nov;18(5):3759-3766. doi: 10.3892/etm.2019.8006. Epub 2019 Sep 13.
• [18] Thymosin beta-10 is aberrantly expressed in pancreatic cancer and induces JNK activation.Cancer Invest. 2009 Mar;27(3):251-6. doi: 10.1080/07357900802254016.
• [19] 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.
• [20] 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.
• [21] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [22] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [23] 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.
• [24] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [25] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [26] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [27] 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.
• [28] 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.
• [29] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [30] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [31] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [32] 5-Fluorouracil: identification of novel downstream mediators of tumour response. Anticancer Res. 2004 Mar-Apr;24(2A):417-23.
• [33] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [34] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [35] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [36] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [37] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [38] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [39] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [40] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [41] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.