Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4NYNO8)

• DOT Name: Serine/threonine-protein kinase 17B (STK17B)
• Synonyms: EC 2.7.11.1; DAP kinase-related apoptosis-inducing protein kinase 2
• Gene Name: STK17B
• Related Disease:
  Breast neoplasm
  Autoimmune disease
  Colorectal carcinoma
  Hepatocellular carcinoma
  Multiple sclerosis
  Neoplasm
  Primary cutaneous T-cell lymphoma
  Thyroid gland carcinoma
  Thyroid gland papillary carcinoma
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: ST17B_HUMAN
• PDB ID: 3LM0; 3LM5; 6QF4; 6Y6F; 6Y6H; 6ZJF; 7AKG; 7Q7C; 7Q7D; 7Q7E
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MSRRRFDCRSISGLLTTTPQIPIKMENFNNFYILTSKELGRGKFAVVRQCISKSTGQEYA
  AKFLKKRRRGQDCRAEILHEIAVLELAKSCPRVINLHEVYENTSEIILILEYAAGGEIFS
  LCLPELAEMVSENDVIRLIKQILEGVYYLHQNNIVHLDLKPQNILLSSIYPLGDIKIVDF
  GMSRKIGHACELREIMGTPEYLAPEILNYDPITTATDMWNIGIIAYMLLTHTSPFVGEDN
  QETYLNISQVNVDYSEETFSSVSQLATDFIQSLLVKNPEKRPTAEICLSHSWLQQWDFEN
  LFHPEETSSSSQTQDHSVRSSEDKTSKSSCNGTCGDREDKENIPEDSSMVSKRFRFDDSL
  PNPHELVSDLLC
• Function: Phosphorylates myosin light chains. Acts as a positive regulator of apoptosis.
• Tissue Specificity: Highly expressed in placenta, lung, pancreas. Lower levels in heart, brain, liver, skeletal muscle and kidney.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[1]
Autoimmune disease	DISORMTM	Limited	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[4]
Multiple sclerosis	DISB2WZI	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]
Primary cutaneous T-cell lymphoma	DIS35WVW	Limited	Biomarker	[5]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[6]
Thyroid gland papillary carcinoma	DIS48YMM	Limited	Biomarker	[6]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[2]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Serine/threonine-protein kinase 17B (STK17B).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[14]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[13]
Marinol	DM70IK5	Approved	Marinol increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[17]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Serine/threonine-protein kinase 17B (STK17B).	[18]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[20]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[21]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Serine/threonine-protein kinase 17B (STK17B).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase 17B (STK17B).	[25]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Serine/threonine-protein kinase 17B (STK17B).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Serine/threonine-protein kinase 17B (STK17B).	[29]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Serine/threonine-protein kinase 17B (STK17B).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Serine/threonine-protein kinase 17B (STK17B).	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Serine/threonine-protein kinase 17B (STK17B).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Serine/threonine-protein kinase 17B (STK17B).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Serine/threonine-protein kinase 17B (STK17B).	[26]

References

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• [4] STK17B promotes carcinogenesis and metastasis via AKT/GSK-3/Snail signaling in hepatocellular carcinoma.Cell Death Dis. 2018 Feb 14;9(2):236. doi: 10.1038/s41419-018-0262-1.
• [5] Identification of selectively expressed genes and antigens in CTCL.Exp Dermatol. 2008 Apr;17(4):324-34. doi: 10.1111/j.1600-0625.2007.00637.x. Epub 2007 Nov 2.
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• [7] Discovery of benzofuran-3(2H)-one derivatives as novel DRAK2 inhibitors that protect islet -cells from apoptosis.Eur J Med Chem. 2017 Apr 21;130:195-208. doi: 10.1016/j.ejmech.2017.02.048. Epub 2017 Feb 21.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [12] 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.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] 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.
• [15] 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.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [17] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [18] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [19] 5-Aza-2'-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer). Biochem Biophys Res Commun. 2006 Dec 15;351(2):455-61. doi: 10.1016/j.bbrc.2006.10.055. Epub 2006 Oct 18.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [22] Resveratrol-induced gene expression profiles in human prostate cancer cells. Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):596-604. doi: 10.1158/1055-9965.EPI-04-0398.
• [23] 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.
• [24] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [25] 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.
• [26] 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.
• [27] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [28] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [29] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [30] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.