Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9HPLP3)

• DOT Name: Thymosin beta-4 (TMSB4X)
• Synonyms: T beta-4; Fx
• Gene Name: TMSB4X
• UniProt ID: TYB4_HUMAN
• PDB ID: 3TU5; 4PL7; 4PL8
• Pfam ID: PF01290
• Sequence: MSDKPDMAEIEKFDKSKLKKTETQEKNPLPSKETIEQEKQAGES
• Function: Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization ; [Hemoregulatory peptide AcSDKP]: Potent inhibitor of bone marrow derived stem cell differentiation. Acts by inhibits the entry of hematopoietic pluripotent stem cells into the S-phase.
• Tissue Specificity: Expressed in several hemopoietic cell lines and lymphoid malignant cells. Decreased levels in myeloma cells.
• KEGG Pathway: Regulation of actin cytoskeleton (hsa04810)
• Reactome Pathway: Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Thymosin beta-4 (TMSB4X) decreases the response to substance of Etoposide.	[17]

3 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-4 (TMSB4X).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Thymosin beta-4 (TMSB4X).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Thymosin beta-4 (TMSB4X).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Thymosin beta-4 (TMSB4X).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Thymosin beta-4 (TMSB4X).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thymosin beta-4 (TMSB4X).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Thymosin beta-4 (TMSB4X).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Thymosin beta-4 (TMSB4X).	[7]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Thymosin beta-4 (TMSB4X).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Thymosin beta-4 (TMSB4X).	[9]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Thymosin beta-4 (TMSB4X).	[10]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Thymosin beta-4 (TMSB4X).	[11]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Thymosin beta-4 (TMSB4X).	[12]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of Thymosin beta-4 (TMSB4X).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Thymosin beta-4 (TMSB4X).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Thymosin beta-4 (TMSB4X).	[9]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Thymosin beta-4 (TMSB4X).	[15]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Thymosin beta-4 (TMSB4X).	[16]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Thymosin beta-4 (TMSB4X).	[2]
SC-560	DMT1GJL	Investigative	SC-560 increases the expression of Thymosin beta-4 (TMSB4X).	[11]

References

• [1] 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.
• [2] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [3] 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.
• [4] 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.
• [5] Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells. Biochemistry. 2007 Aug 7;46(31):8920-32. doi: 10.1021/bi7000328. Epub 2007 Jul 14.
• [6] 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.
• [7] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [8] 5-Fluorouracil: identification of novel downstream mediators of tumour response. Anticancer Res. 2004 Mar-Apr;24(2A):417-23.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [11] Selective nonsteroidal anti-inflammatory drugs induce thymosin beta-4 and alter actin cytoskeletal organization in human colorectal cancer cells. J Pharmacol Exp Ther. 2004 Dec;311(3):885-91. doi: 10.1124/jpet.104.070664. Epub 2004 Aug 3.
• [12] Downregulation of thymosin beta4 expression by androgen in prostate cancer LNCaP cells. J Androl. 2008 Mar-Apr;29(2):207-12. doi: 10.2164/jandrol.107.003608. Epub 2007 Oct 3.
• [13] 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.
• [14] 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.
• [15] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [16] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
• [17] Overexpression of thymosin beta-4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating Survivin expression, respectively. Carcinogenesis. 2006 May;27(5):936-44. doi: 10.1093/carcin/bgi316. Epub 2005 Dec 19.