Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI00JVW)

• DOT Name: Serine/threonine-protein kinase 38-like (STK38L)
• Synonyms: EC 2.7.11.1; NDR2 protein kinase; Nuclear Dbf2-related kinase 2
• Gene Name: STK38L
• UniProt ID: ST38L_HUMAN
• PDB ID: 5XQZ
• EC Number: 2.7.11.1
• Pfam ID: PF00069 ; PF00433
• Sequence:
  MAMTAGTTTTFPMSNHTRERVTVAKLTLENFYSNLILQHEERETRQKKLEVAMEEEGLAD
  EEKKLRRSQHARKETEFLRLKRTRLGLDDFESLKVIGRGAFGEVRLVQKKDTGHIYAMKI
  LRKSDMLEKEQVAHIRAERDILVEADGAWVVKMFYSFQDKRNLYLIMEFLPGGDMMTLLM
  KKDTLTEEETQFYISETVLAIDAIHQLGFIHRDIKPDNLLLDAKGHVKLSDFGLCTGLKK
  AHRTEFYRNLTHNPPSDFSFQNMNSKRKAETWKKNRRQLAYSTVGTPDYIAPEVFMQTGY
  NKLCDWWSLGVIMYEMLIGYPPFCSETPQETYRKVMNWKETLVFPPEVPISEKAKDLILR
  FCIDSENRIGNSGVEEIKGHPFFEGVDWEHIRERPAAIPIEIKSIDDTSNFDDFPESDIL
  QPVPNTTEPDYKSKDWVFLNYTYKRFEGLTQRGSIPTYMKAGKL
• Function: Involved in the regulation of structural processes in differentiating and mature neuronal cells.
• Tissue Specificity: Ubiquitously expressed with highest levels observed in the thymus.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Serine/threonine-protein kinase 38-like (STK38L).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Serine/threonine-protein kinase 38-like (STK38L).	[5]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Serine/threonine-protein kinase 38-like (STK38L).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[6]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[7]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Serine/threonine-protein kinase 38-like (STK38L).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[14]
Myricetin	DMTV4L0	Investigative	Myricetin decreases the expression of Serine/threonine-protein kinase 38-like (STK38L).	[15]

References

• [1] 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.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [11] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [12] 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.
• [13] 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.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] Potential role of nucleoside diphosphate kinase in myricetin-induced selective apoptosis in colon cancer HCT-15?cells. Food Chem Toxicol. 2018 Jun;116(Pt B):315-322. doi: 10.1016/j.fct.2018.04.053. Epub 2018 Apr 24.