Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDJ4RV0)

• DOT Name: Stathmin (STMN1)
• Synonyms: Leukemia-associated phosphoprotein p18; Metablastin; Oncoprotein 18; Op18; Phosphoprotein p19; pp19; Prosolin; Protein Pr22; pp17
• Gene Name: STMN1
• UniProt ID: STMN1_HUMAN
• Pfam ID: PF00836
• Sequence:
  MASSDIQVKELEKRASGQAFELILSPRSKESVPEFPLSPPKKKDLSLEEIQKKLEAAEER
  RKSHEAEVLKQLAEKREHEKEVLQKAIEENNNFSKMAEEKLTHKMEANKENREAQMAAKL
  ERLREKDKHIEEVRKNKESKDPADETEAD
• Function: Involved in the regulation of the microtubule (MT) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Phosphorylation at Ser-16 may be required for axon formation during neurogenesis. Involved in the control of the learned and innate fear.
• Tissue Specificity: Ubiquitous. Expression is strongest in fetal and adult brain, spinal cord, and cerebellum, followed by thymus, bone marrow, testis, and fetal liver. Expression is intermediate in colon, ovary, placenta, uterus, and trachea, and is readily detected at substantially lower levels in all other tissues examined. Lowest expression is found in adult liver. Present in much greater abundance in cells from patients with acute leukemia of different subtypes than in normal peripheral blood lymphocytes, non-leukemic proliferating lymphoid cells, bone marrow cells, or cells from patients with chronic lymphoid or myeloid leukemia.
• KEGG Pathway:
  MAPK sig.ling pathway (hsa04010)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway: Nuclear signaling by ERBB4 (R-HSA-1251985)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Etoposide	DMNH3PG	Approved	Stathmin (STMN1) affects the response to substance of Etoposide.	[37]
Paclitaxel	DMLB81S	Approved	Stathmin (STMN1) affects the response to substance of Paclitaxel.	[37]
DTI-015	DMXZRW0	Approved	Stathmin (STMN1) affects the response to substance of DTI-015.	[38]
Lomustine	DMMWSUL	Approved	Stathmin (STMN1) affects the response to substance of Lomustine.	[38]

37 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 (STMN1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Stathmin (STMN1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Stathmin (STMN1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Stathmin (STMN1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Stathmin (STMN1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Stathmin (STMN1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Stathmin (STMN1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Stathmin (STMN1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Stathmin (STMN1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Stathmin (STMN1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Stathmin (STMN1).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Stathmin (STMN1).	[12]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Stathmin (STMN1).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Stathmin (STMN1).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Stathmin (STMN1).	[14]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Stathmin (STMN1).	[15]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Stathmin (STMN1).	[16]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Stathmin (STMN1).	[17]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Stathmin (STMN1).	[13]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Stathmin (STMN1).	[18]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Stathmin (STMN1).	[19]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Stathmin (STMN1).	[20]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Stathmin (STMN1).	[21]
Sertraline	DM0FB1J	Approved	Sertraline decreases the expression of Stathmin (STMN1).	[22]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Stathmin (STMN1).	[23]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Stathmin (STMN1).	[24]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Stathmin (STMN1).	[25]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Stathmin (STMN1).	[26]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Stathmin (STMN1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Stathmin (STMN1).	[28]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Stathmin (STMN1).	[29]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Stathmin (STMN1).	[30]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Stathmin (STMN1).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Stathmin (STMN1).	[33]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Stathmin (STMN1).	[34]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Stathmin (STMN1).	[35]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Stathmin (STMN1).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
G1	DMTV42K	Phase 1/2	G1 decreases the phosphorylation of Stathmin (STMN1).	[27]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Stathmin (STMN1).	[31]

References

• [1] 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.
• [2] 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.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Impact of cisplatin administration on protein expression levels in renal cell carcinoma: a proteomic analysis. Eur J Pharmacol. 2011 Nov 16;670(1):50-7. doi: 10.1016/j.ejphar.2011.08.030. Epub 2011 Sep 8.
• [7] 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.
• [8] 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.
• [9] Protein expression profiling identifies molecular targets of quercetin as a major dietary flavonoid in human colon cancer cells. Proteomics. 2004 Jul;4(7):2160-74.
• [10] Stathmin is involved in arsenic trioxide-induced apoptosis in human cervical cancer cell lines via PI3K linked signal pathway. Cancer Biol Ther. 2010 Sep 15;10(6):632-43. doi: 10.4161/cbt.10.6.12654. Epub 2010 Sep 13.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [13] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [14] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [15] Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells. J Cell Biochem. 2006 Aug 1;98(5):1163-84.
• [16] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [17] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [18] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [19] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [20] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [21] Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells. Mol Cancer Ther. 2012 Oct;11(10):2138-48. doi: 10.1158/1535-7163.MCT-12-0562. Epub 2012 Aug 6.
• [22] Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
• [23] Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics. Toxicol Lett. 2017 Nov 5;281:26-34. doi: 10.1016/j.toxlet.2017.09.001. Epub 2017 Sep 5.
• [24] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [25] Comparative proteomics reveals concordant and discordant biochemical effects of caffeine versus epigallocatechin-3-gallate in human endothelial cells. Toxicol Appl Pharmacol. 2019 Sep 1;378:114621. doi: 10.1016/j.taap.2019.114621. Epub 2019 Jun 10.
• [26] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [27] The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
• [28] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [29] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [30] 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.
• [31] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [32] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [35] 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.
• [36] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [37] Therapeutic interactions between stathmin inhibition and chemotherapeutic agents in prostate cancer. Mol Cancer Ther. 2006 Dec;5(12):3248-57. doi: 10.1158/1535-7163.MCT-06-0227.
• [38] The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas. J Natl Cancer Inst. 2007 Apr 18;99(8):639-52. doi: 10.1093/jnci/djk135.