Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS87MOT)

• DOT Name: Serine/threonine-protein kinase 17A (STK17A)
• Synonyms: EC 2.7.11.1; DAP kinase-related apoptosis-inducing protein kinase 1
• Gene Name: STK17A
• UniProt ID: ST17A_HUMAN
• PDB ID: 7QUE; 7QUF
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MIPLEKPGSGGSSPGATSGSGRAGRGLSGPCRPPPPPQARGLLTEIRAVVRTEPFQDGYS
  LCPGRELGRGKFAVVRKCIKKDSGKEFAAKFMRKRRKGQDCRMEIIHEIAVLELAQDNPW
  VINLHEVYETASEMILVLEYAAGGEIFDQCVADREEAFKEKDVQRLMRQILEGVHFLHTR
  DVVHLDLKPQNILLTSESPLGDIKIVDFGLSRILKNSEELREIMGTPEYVAPEILSYDPI
  SMATDMWSIGVLTYVMLTGISPFLGNDKQETFLNISQMNLSYSEEEFDVLSESAVDFIRT
  LLVKKPEDRATAEECLKHPWLTQSSIQEPSFRMEKALEEANALQEGHSVPEINSDTDKSE
  TKESIVTEELIVVTSYTLGQCRQSEKEKMEQKAISKRFKFEEPLLQEIPGEFIY
• Function: Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.
• Tissue Specificity: Highly expressed in placenta. Lower levels in heart, lung, skeletal muscle, kidney and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

21 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 17A (STK17A).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Serine/threonine-protein kinase 17A (STK17A).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Serine/threonine-protein kinase 17A (STK17A).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine/threonine-protein kinase 17A (STK17A).	[11]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Serine/threonine-protein kinase 17A (STK17A).	[12]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Serine/threonine-protein kinase 17A (STK17A).	[13]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Serine/threonine-protein kinase 17A (STK17A).	[14]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[16]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/threonine-protein kinase 17A (STK17A).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Serine/threonine-protein kinase 17A (STK17A).	[21]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Serine/threonine-protein kinase 17A (STK17A).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Serine/threonine-protein kinase 17A (STK17A).	[18]

References

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• [2] 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.
• [3] 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.
• [4] 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.
• [5] Identification of novel biomarkers for doxorubicin-induced toxicity in human cardiomyocytes derived from pluripotent stem cells. Toxicology. 2015 Feb 3;328:102-11. doi: 10.1016/j.tox.2014.12.018. Epub 2014 Dec 18.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] 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.
• [8] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [9] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [10] 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.
• [11] 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.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [14] 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.
• [15] 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.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [18] 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.
• [19] 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.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.