Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT20F289)

• DOT Name: Stathmin-3 (STMN3)
• Synonyms: SCG10-like protein
• Gene Name: STMN3
• Related Disease:
  Adult glioblastoma
  Glioblastoma multiforme
  Glioma
  Adenocarcinoma
  Neoplasm
  Non-small-cell lung cancer
  Squamous cell carcinoma
• UniProt ID: STMN3_HUMAN
• Pfam ID: PF00836
• Sequence:
  MASTISAYKEKMKELSVLSLICSCFYTQPHPNTVYQYGDMEVKQLDKRASGQSFEVILKS
  PSDLSPESPMLSSPPKKKDTSLEELQKRLEAAEERRKTQEAQVLKQLAERREHEREVLHK
  ALEENNNFSRQAEEKLNYKMELSKEIREAHLAALRERLREKELHAAEVRRNKEQREEMSG
• Function: Exhibits microtubule-destabilizing activity, which is antagonized by STAT3.
• Tissue Specificity: Neuron specific.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[2]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]
Non-small-cell lung cancer	DIS5Y6R9	Limited	Altered Expression	[2]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[2]

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 Stathmin-3 (STMN3).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Stathmin-3 (STMN3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Stathmin-3 (STMN3).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Stathmin-3 (STMN3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Stathmin-3 (STMN3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen affects the expression of Stathmin-3 (STMN3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Stathmin-3 (STMN3).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Stathmin-3 (STMN3).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Stathmin-3 (STMN3).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Stathmin-3 (STMN3).	[11]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Stathmin-3 (STMN3).	[12]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Stathmin-3 (STMN3).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Stathmin-3 (STMN3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Stathmin-3 (STMN3).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Stathmin-3 (STMN3).	[16]

References

• [1] Overexpression of SCLIP promotes growth and motility in glioblastoma cells.Cancer Biol Ther. 2015;16(1):97-105. doi: 10.4161/15384047.2014.987037.
• [2] Coordinated expression of stathmin family members by far upstream sequence element-binding protein-1 increases motility in non-small cell lung cancer.Cancer Res. 2009 Mar 15;69(6):2234-43. doi: 10.1158/0008-5472.CAN-08-3338. Epub 2009 Mar 3.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors. Toxicol In Vitro. 2015 Sep;29(6):1231-9. doi: 10.1016/j.tiv.2014.10.012. Epub 2014 Oct 24.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] 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.
• [12] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] 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.
• [16] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.