Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT1313J)

• DOT Name: STE20-like serine/threonine-protein kinase (SLK)
• Synonyms: STE20-like kinase; hSLK; EC 2.7.11.1; CTCL tumor antigen se20-9; STE20-related serine/threonine-protein kinase; STE20-related kinase; Serine/threonine-protein kinase 2
• Gene Name: SLK
• UniProt ID: SLK_HUMAN
• PDB ID: 2J51; 2JFL; 2JFM; 2UV2; 4USF; 6HVD; 8BEM
• EC Number: 2.7.11.1
• Pfam ID: PF00069 ; PF12474
• Sequence:
  MSFFNFRKIFKLGSEKKKKQYEHVKRDLNPEDFWEIIGELGDGAFGKVYKAQNKETSVLA
  AAKVIDTKSEEELEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFCAGGAVDAVM
  LELERPLTESQIQVVCKQTLDALNYLHDNKIIHRDLKAGNILFTLDGDIKLADFGVSAKN
  TRTIQRRDSFIGTPYWMAPEVVMCETSKDRPYDYKADVWSLGITLIEMAEIEPPHHELNP
  MRVLLKIAKSEPPTLAQPSRWSSNFKDFLKKCLEKNVDARWTTSQLLQHPFVTVDSNKPI
  RELIAEAKAEVTEEVEDGKEEDEEEETENSLPIPASKRASSDLSIASSEEDKLSQNACIL
  ESVSEKTERSNSEDKLNSKILNEKPTTDEPEKAVEDINEHITDAQLEAMTELHDRTAVIK
  ENEREKRPKLENLPDTEDQETVDINSVSEGKENNIMITLETNIEHNLKSEEEKDQEKQQM
  FENKLIKSEEIKDTILQTVDLVSQETGEKEANIQAVDSEVGLTKEDTQEKLGEDDKTQKD
  VISNTSDVIGTCEAADVAQKVDEDSAEDTQSNDGKEVVEVGQKLINKPMVGPEAGGTKEV
  PIKEIVEMNEIEEGKNKEQAINSSENIMDINEEPGTTEGEEITESSSTEEMEVRSVVADT
  DQKALGSEVQDASKVTTQIDKEKKEIPVSIKKEPEVTVVSQPTEPQPVLIPSININSDSG
  ENKEEIGSLSKTETILPPESENPKENDNDSGTGSTADTSSIDLNLSISSFLSKTKDSGSI
  SLQETRRQKKTLKKTRKFIVDGVEVSVTTSKIVTDSDSKTEELRFLRRQELRELRFLQKE
  EQRAQQQLNSKLQQQREQIFRRFEQEMMSKKRQYDQEIENLEKQQKQTIERLEQEHTNRL
  RDEAKRIKGEQEKELSKFQNMLKNRKKEVINEVEKAPKELRKELMKRRKEELAQSQHAQE
  QEFVQKQQQELDGSLKKIIQQQKAELANIERECLNNKQQLMRAREAAIWELEERHLQEKH
  QLLKQQLKDQYFMQRHQLLKRHEKETEQMQRYNQRLIEELKNRQTQERARLPKIQRSEAK
  TRMAMFKKSLRINSTATPDQDRDKIKQFAAQEEKRQKNERMAQHQKHENQMRDLQLQCEA
  NVRELHQLQNEKCHLLVEHETQKLKELDEEHSQELKEWREKLRPRKKTLEEEFARKLQEQ
  EVFFKMTGESECLNPSTQSRISKFYPIPSLHSTGS
• Function: Mediates apoptosis and actin stress fiber dissolution.
• Tissue Specificity: Ubiquitously expressed. Highest expression is found in heart and in skeletal muscle.
• KEGG Pathway: Oocyte meiosis (hsa04114)
• Reactome Pathway:
  RHOB GTPase cycle (R-HSA-9013026)
  RHOC GTPase cycle (R-HSA-9013106)
  RHOA GTPase cycle (R-HSA-8980692)

Molecular Interaction Atlas (MIA) of This DOT

11 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 STE20-like serine/threonine-protein kinase (SLK).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of STE20-like serine/threonine-protein kinase (SLK).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of STE20-like serine/threonine-protein kinase (SLK).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of STE20-like serine/threonine-protein kinase (SLK).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of STE20-like serine/threonine-protein kinase (SLK).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of STE20-like serine/threonine-protein kinase (SLK).	[6]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of STE20-like serine/threonine-protein kinase (SLK).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of STE20-like serine/threonine-protein kinase (SLK).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of STE20-like serine/threonine-protein kinase (SLK).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of STE20-like serine/threonine-protein kinase (SLK).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of STE20-like serine/threonine-protein kinase (SLK).	[12]

3 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 affects the phosphorylation of STE20-like serine/threonine-protein kinase (SLK).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of STE20-like serine/threonine-protein kinase (SLK).	[10]
Octanal	DMTN0OK	Investigative	Octanal increases the methylation of STE20-like serine/threonine-protein kinase (SLK).	[13]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] 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.
• [6] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [7] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [8] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [9] Benzo[a]pyrene-induced DNA damage associated with mutagenesis in primary human activated T lymphocytes. Biochem Pharmacol. 2017 Aug 1;137:113-124.
• [10] 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.
• [11] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.