Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW4QE0D)

• DOT Name: Serine/threonine-protein kinase 26 (STK26)
• Synonyms: EC 2.7.11.1; MST3 and SOK1-related kinase; Mammalian STE20-like protein kinase 4; MST-4; STE20-like kinase MST4; Serine/threonine-protein kinase MASK
• Gene Name: STK26
• Related Disease:
  Gastric cancer
  Stomach cancer
  Advanced cancer
  Allergic rhinitis
  Cerebral infarction
  Graves disease
  Hepatocellular carcinoma
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Rhinitis
  Polycystic ovarian syndrome
  Glioblastoma multiforme
• UniProt ID: STK26_HUMAN
• PDB ID: 3GGF; 3W8I; 4FZA; 4FZD; 4FZF; 4GEH; 5XY9; 5YF4; 7B36
• EC Number: 2.7.11.1
• Pfam ID: PF20929 ; PF00069
• Sequence:
  MAHSPVAVQVPGMQNNIADPEELFTKLERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEA
  EDEIEDIQQEITVLSQCDSSYVTKYYGSYLKGSKLWIIMEYLGGGSALDLLRAGPFDEFQ
  IATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFV
  GTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLFLIPKNNPPTLV
  GDFTKSFKEFIDACLNKDPSFRPTAKELLKHKFIVKNSKKTSYLTELIDRFKRWKAEGHS
  DDESDSEGSDSESTSRENNTHPEWSFTTVRKKPDPKKVQNGAEQDLVQTLSCLSMIITPA
  FAELKQQDENNASRNQAIEELEKSIAVAEAACPGITDKMVKKLIEKFQKCSADESP
• Function: Serine/threonine-protein kinase that acts as a mediator of cell growth. Modulates apoptosis. In association with STK24 negatively regulates Golgi reorientation in polarized cell migration upon RHO activation. Phosphorylates ATG4B at 'Ser-383', thereby increasing autophagic flux.
• Reactome Pathway: Apoptotic cleavage of cellular proteins (R-HSA-111465)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Biomarker	[1]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[3]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[4]
Graves disease	DISU4KOQ	Strong	Altered Expression	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[7]
Rhinitis	DISKLMN7	Strong	Biomarker	[8]
Polycystic ovarian syndrome	DISZ2BNG	moderate	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Disputed	Biomarker	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Serine/threonine-protein kinase 26 (STK26) affects the response to substance of Doxorubicin.	[26]
Vinblastine	DM5TVS3	Approved	Serine/threonine-protein kinase 26 (STK26) affects the response to substance of Vinblastine.	[26]

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 Serine/threonine-protein kinase 26 (STK26).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Serine/threonine-protein kinase 26 (STK26).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Serine/threonine-protein kinase 26 (STK26).	[25]

15 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 Serine/threonine-protein kinase 26 (STK26).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/threonine-protein kinase 26 (STK26).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein kinase 26 (STK26).	[13]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/threonine-protein kinase 26 (STK26).	[14]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine/threonine-protein kinase 26 (STK26).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/threonine-protein kinase 26 (STK26).	[16]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine/threonine-protein kinase 26 (STK26).	[17]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serine/threonine-protein kinase 26 (STK26).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Serine/threonine-protein kinase 26 (STK26).	[19]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Serine/threonine-protein kinase 26 (STK26).	[20]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine/threonine-protein kinase 26 (STK26).	[21]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Serine/threonine-protein kinase 26 (STK26).	[15]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene decreases the expression of Serine/threonine-protein kinase 26 (STK26).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase 26 (STK26).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/threonine-protein kinase 26 (STK26).	[24]

References

• [1] MST4 Predicts Poor Prognosis And Promotes Metastasis By Facilitating Epithelial-Mesenchymal Transition In Gastric Cancer.Cancer Manag Res. 2019 Nov 5;11:9353-9369. doi: 10.2147/CMAR.S219689. eCollection 2019.
• [2] MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma.Cancer Cell. 2017 Dec 11;32(6):840-855.e8. doi: 10.1016/j.ccell.2017.11.005.
• [3] Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.J Allergy Clin Immunol. 2019 Jul;144(1):135-143.e6. doi: 10.1016/j.jaci.2019.01.053. Epub 2019 Apr 3.
• [4] MST4 modulates the neuro-inflammatory response by regulating IB signaling pathway and affects the early outcome of experimental ischemic stroke in mice.Brain Res Bull. 2020 Jan;154:43-50. doi: 10.1016/j.brainresbull.2019.10.011. Epub 2019 Nov 10.
• [5] MST-4 and TRAF-6 expression in the peripheral blood mononuclear cells of patients with Graves' disease and its significance.BMC Endocr Disord. 2017 Feb 20;17(1):11. doi: 10.1186/s12902-017-0161-y.
• [6] MST4 promotes hepatocellular carcinoma epithelial-mesenchymal transition and metastasis via activation of the p-ERK pathway.Int J Oncol. 2014 Aug;45(2):629-40. doi: 10.3892/ijo.2014.2455. Epub 2014 May 22.
• [7] The Ste20 kinase MST4 plays a role in prostate cancer progression.Cancer Res. 2003 Jun 15;63(12):3356-63.
• [8] Interactions Between Air Pollution and Pollen Season for Rhinitis Using Mobile Technology: A MASK-POLLAR Study.J Allergy Clin Immunol Pract. 2020 Mar;8(3):1063-1073.e4. doi: 10.1016/j.jaip.2019.11.022. Epub 2019 Nov 28.
• [9] MicroRNA-486-5p inhibits ovarian granulosa cell proliferation and participates in the development of PCOS via targeting MST4.Eur Rev Med Pharmacol Sci. 2019 Sep;23(17):7217-7223. doi: 10.26355/eurrev_201909_18823.
• [10] 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.
• [11] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [12] 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.
• [13] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [17] 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.
• [18] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [19] 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.
• [20] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [21] 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.
• [22] 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.
• [23] 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.
• [24] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [25] 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.
• [26] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.