Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTISF4KG)

• DOT Name: Serine/threonine-protein kinase PDIK1L (PDIK1L)
• Synonyms: EC 2.7.11.1; PDLIM1-interacting kinase 1-like
• Gene Name: PDIK1L
• Related Disease:
  Glioblastoma multiforme
  Neuroblastoma
  Non-insulin dependent diabetes
  Acute myocardial infarction
  Adult glioblastoma
  Advanced cancer
  Arteriosclerosis
  Astrocytoma
  Atherosclerosis
  B-cell neoplasm
  Breast cancer
  Breast carcinoma
  Colon cancer
  Colon carcinoma
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Medulloblastoma
  Multiple sclerosis
  Myelodysplastic syndrome
  Neoplasm
  Non-small-cell lung cancer
  Prion disease
  Progressive multifocal leukoencephalopathy
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
  Small lymphocytic lymphoma
  Triple negative breast cancer
  Melanoma
  Acute lymphocytic leukaemia
  Parkinson disease
  Alzheimer disease
  Colorectal carcinoma
  Endometrial carcinoma
  Familial adenomatous polyposis
  Gastric cancer
  Intellectual disability
  Lung neoplasm
  Pancreatic cancer
  Stomach cancer
  Stroke
  T-cell acute lymphoblastic leukaemia
  Type-1/2 diabetes
• UniProt ID: PDK1L_HUMAN
• EC Number: 2.7.11.1
• Pfam ID: PF00069
• Sequence:
  MVSSQPKYDLIREVGRGSYGVVYEAVIRKTSARVAVKKIRCHAPENVELALREFWALSSI
  KSQHPNVIHLEECILQKDGMVQKMSHGSNSSLYLQLVETSLKGEIAFDPRSAYYLWFVMD
  FCDGGDMNEYLLSRKPNRKTNTSFMLQLSSALAFLHKNQIIHRDLKPDNILISQTRLDTS
  DLEPTLKVADFGLSKVCSASGQNPEEPVSVNKCFLSTACGTDFYMAPEVWEGHYTAKADI
  FALGIIIWAMLERITFIDTETKKELLGSYVKQGTEIVPVGEALLENPKMELLIPVKKKSM
  NGRMKQLIKEMLAANPQDRPDAFELELRLVQIAFKDSSWET
• Tissue Specificity: Expressed in liver, kidney, pancreas, spleen, thymus and prostate.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[1]
Neuroblastoma	DISVZBI4	Definitive	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Biomarker	[3]
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[5]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[6]
Astrocytoma	DISL3V18	Strong	Biomarker	[7]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[6]
B-cell neoplasm	DISVY326	Strong	Biomarker	[8]
Breast cancer	DIS7DPX1	Strong	Biomarker	[9]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[9]
Colon cancer	DISVC52G	Strong	Biomarker	[10]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[10]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
leukaemia	DISS7D1V	Strong	Genetic Variation	[14]
Leukemia	DISNAKFL	Strong	Altered Expression	[15]
Lung cancer	DISCM4YA	Strong	Biomarker	[16]
Lung carcinoma	DISTR26C	Strong	Biomarker	[16]
Medulloblastoma	DISZD2ZL	Strong	Biomarker	[17]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[18]
Myelodysplastic syndrome	DISYHNUI	Strong	Genetic Variation	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[20]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[21]
Prion disease	DISOUMB0	Strong	Biomarker	[22]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[23]
Prostate cancer	DISF190Y	Strong	Altered Expression	[24]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[24]
Schizophrenia	DISSRV2N	Strong	Biomarker	[25]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[26]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[27]
Melanoma	DIS1RRCY	moderate	Biomarker	[28]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Posttranslational Modification	[15]
Parkinson disease	DISQVHKL	Disputed	Biomarker	[29]
Alzheimer disease	DISF8S70	Limited	Biomarker	[30]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[31]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[32]
Familial adenomatous polyposis	DISW53RE	Limited	Biomarker	[33]
Gastric cancer	DISXGOUK	Limited	Biomarker	[34]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[35]
Lung neoplasm	DISVARNB	Limited	Biomarker	[16]
Pancreatic cancer	DISJC981	Limited	Biomarker	[36]
Stomach cancer	DISKIJSX	Limited	Biomarker	[34]
Stroke	DISX6UHX	Limited	Biomarker	[37]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Biomarker	[38]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[39]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[40]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[41]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[42]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[43]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Serine/threonine-protein kinase PDIK1L (PDIK1L).	[47]

References

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• [2] Ethanol induces cell cycle arrest and triggers apoptosis via Sp1-dependent p75NTR expression in human neuroblastoma cells.Cell Biol Toxicol. 2013 Oct;29(5):365-80. doi: 10.1007/s10565-013-9260-3. Epub 2013 Sep 12.
• [3] Casein kinase 2 phosphorylates and stabilizes C/EBP in pancreatic cells.Biochem Biophys Res Commun. 2018 Feb 26;497(1):451-456. doi: 10.1016/j.bbrc.2018.02.108. Epub 2018 Feb 12.
• [4] Protective effect of diethylcarbamazine inhibits NF-B activation in isoproterenol-induced acute myocardial infarction rat model through the PARP pathway.Mol Med Rep. 2017 Aug;16(2):1596-1602. doi: 10.3892/mmr.2017.6695. Epub 2017 Jun 6.
• [5] Chronic cadmium exposure aggravates malignant phenotypes of nasopharyngeal carcinoma by activating the Wnt/-catenin signaling pathway via hypermethylation of the casein kinase 1 promoter.Cancer Manag Res. 2018 Dec 19;11:81-93. doi: 10.2147/CMAR.S171200. eCollection 2019.
• [6] Critical role for casein kinase 2 and phosphoinositide-3-kinase in the interferon-gamma-induced expression of monocyte chemoattractant protein-1 and other key genes implicated in atherosclerosis.Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):806-12. doi: 10.1161/01.ATV.0000258867.79411.96. Epub 2007 Jan 25.
• [7] Novel small molecule protein kinase CK2 inhibitors exert potent antitumor effects on T98G and SEGA cells in vitro.Folia Neuropathol. 2019;57(3):239-248. doi: 10.5114/fn.2019.88452.
• [8] Activation of Casein Kinase II by Gallic Acid Induces BIK-BAX/BAK-Mediated ER Ca(++)-ROS-Dependent Apoptosis of Human Oral Cancer Cells.Front Physiol. 2017 Sep 29;8:761. doi: 10.3389/fphys.2017.00761. eCollection 2017.
• [9] Silencing of casein kinase 2 inhibits PKCinduced cell invasion by targeting MMP? in MCF? cells.Mol Med Rep. 2018 Jun;17(6):8397-8402. doi: 10.3892/mmr.2018.8885. Epub 2018 Apr 13.
• [10] Pharmacological Inhibition of Casein Kinase 2 Enhances the Effectiveness of PI3K Inhibition in Colon Cancer Cells.Anticancer Res. 2018 Nov;38(11):6195-6200. doi: 10.21873/anticanres.12973.
• [11] Phosphorylation of human La protein at Ser 366 by casein kinase II contributes to hepatitis B virus replication and expression in vitro.J Viral Hepat. 2013 Jan;20(1):24-33. doi: 10.1111/j.1365-2893.2012.01636.x. Epub 2012 Jul 9.
• [12] Induction of Huh? cell apoptosis by HCV core proteins via CK1p53Bid signaling pathway.Mol Med Rep. 2018 Jun;17(6):7559-7566. doi: 10.3892/mmr.2018.8844. Epub 2018 Apr 5.
• [13] The phosphorylation of SEPT2 on Ser218 by casein kinase 2 is important to hepatoma carcinoma cell proliferation.Mol Cell Biochem. 2009 May;325(1-2):61-7. doi: 10.1007/s11010-008-0020-2. Epub 2009 Jan 23.
• [14] Protein signaling and regulation of gene transcription in leukemia: role of the Casein Kinase II-Ikaros axis.J Investig Med. 2016 Mar;64(3):735-9. doi: 10.1136/jim-2016-000075. Epub 2016 Feb 9.
• [15] Combined Casein Kinase II inhibition and epigenetic modulation in acute B-lymphoblastic leukemia.BMC Cancer. 2019 Mar 6;19(1):202. doi: 10.1186/s12885-019-5411-0.
• [16] CIGB-300, an anti-CK2 peptide, inhibits angiogenesis, tumor cell invasion and metastasis in lung cancer models.Lung Cancer. 2017 May;107:14-21. doi: 10.1016/j.lungcan.2016.05.026. Epub 2016 Jun 1.
• [17] Correction: Casein kinase 2 inhibition sensitizes medulloblastoma to temozolomide.Oncogene. 2020 Feb;39(9):2029. doi: 10.1038/s41388-019-1077-y.
• [18] Inhibition of Casein Kinase 2 Protects Oligodendrocytes From Excitotoxicity by Attenuating JNK/p53 Signaling Cascade.Front Mol Neurosci. 2018 Sep 13;11:333. doi: 10.3389/fnmol.2018.00333. eCollection 2018.
• [19] Tumor-derived CK1 mutations enhance MDMX inhibition of p53.Oncogene. 2020 Jan;39(1):176-186. doi: 10.1038/s41388-019-0979-z. Epub 2019 Aug 28.
• [20] Casein kinase 2 inhibition sensitizes medulloblastoma to temozolomide.Oncogene. 2019 Oct;38(42):6867-6879. doi: 10.1038/s41388-019-0927-y. Epub 2019 Aug 12.
• [21] Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non-Small Cell Lung Cancer.Cancer Res. 2015 Nov 15;75(22):4937-48. doi: 10.1158/0008-5472.CAN-15-1113. Epub 2015 Oct 21.
• [22] Protein Misfolding, Signaling Abnormalities and Altered Fast Axonal Transport: Implications for Alzheimer and Prion Diseases.Front Cell Neurosci. 2019 Jul 30;13:350. doi: 10.3389/fncel.2019.00350. eCollection 2019.
• [23] CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor.Mol Cell Biochem. 2008 Sep;316(1-2):149-54. doi: 10.1007/s11010-008-9812-7. Epub 2008 Jun 20.
• [24] CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression.World J Urol. 2017 Aug;35(8):1213-1221. doi: 10.1007/s00345-016-1996-y. Epub 2017 Jan 19.
• [25] Selective knockout of the casein kinase 2 in d1 medium spiny neurons controls dopaminergic function.Biol Psychiatry. 2013 Jul 15;74(2):113-21. doi: 10.1016/j.biopsych.2012.11.013. Epub 2013 Jan 3.
• [26] Casein kinase 1 is a therapeutic target in chronic lymphocytic leukemia. Blood. 2018 Mar 15;131(11):1206-1218.
• [27] Preclinical evaluation of cyclin dependent kinase 11 and casein kinase 2 survival kinases as RNA interference targets for triple negative breast cancer therapy.Breast Cancer Res. 2015;17:19. doi: 10.1186/s13058-015-0524-0. Epub 2015 Feb 11.
• [28] Protein Kinase CK2 Maintains Extracellular Signal-regulated Kinase (ERK) Activity in a CK2 Kinase-independent Manner to Promote Resistance to Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma.J Biol Chem. 2016 Aug 19;291(34):17804-15. doi: 10.1074/jbc.M115.712885. Epub 2016 May 17.
• [29] CK2 Oppositely Modulates l-DOPA-Induced Dyskinesia via Striatal Projection Neurons Expressing D1 or D2 Receptors.J Neurosci. 2017 Dec 6;37(49):11930-11946. doi: 10.1523/JNEUROSCI.0443-17.2017. Epub 2017 Nov 2.
• [30] Inhibition of casein kinase 1/improves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer's disease.Sci Rep. 2019 Sep 24;9(1):13743. doi: 10.1038/s41598-019-50197-x.
• [31] Decreased CK1 expression predicts prolonged survival in colorectal cancer patients.Tumour Biol. 2016 Jul;37(7):8731-9. doi: 10.1007/s13277-015-4745-8. Epub 2016 Jan 7.
• [32] CK2 controls TRAIL and Fas sensitivity by regulating FLIP levels in endometrial carcinoma cells.Oncogene. 2008 Apr 17;27(18):2513-24. doi: 10.1038/sj.onc.1210924. Epub 2007 Nov 5.
• [33] Manilkara zapota (L.) P. Royen leaf water extract triggered apoptosis and activated caspase-dependent pathway in HT-29 human colorectal cancer cell line.Biomed Pharmacother. 2019 Feb;110:748-757. doi: 10.1016/j.biopha.2018.12.027. Epub 2018 Dec 13.
• [34] Inhibiting casein kinase 2 overcomes paclitaxel resistance in gastric cancer.Gastric Cancer. 2019 Nov;22(6):1153-1163. doi: 10.1007/s10120-019-00971-7. Epub 2019 May 16.
• [35] Identification of de novo CSNK2A1 and CSNK2B variants in cases of global developmental delay with seizures.J Hum Genet. 2019 Apr;64(4):313-322. doi: 10.1038/s10038-018-0559-z. Epub 2019 Jan 17.
• [36] Autophagy Induced by CX-4945, a Casein Kinase 2 Inhibitor, Enhances Apoptosis in Pancreatic Cancer Cell Lines.Pancreas. 2017 Apr;46(4):575-581. doi: 10.1097/MPA.0000000000000780.
• [37] Targeting MAPK phosphorylation of Connexin43 provides neuroprotection in stroke.J Exp Med. 2019 Apr 1;216(4):916-935. doi: 10.1084/jem.20171452. Epub 2019 Mar 14.
• [38] Synergistic therapeutic effect of diethylstilbestrol and CX-4945 in human acute T-lymphocytic leukemia cells.Biomed Pharmacother. 2018 Feb;98:357-363. doi: 10.1016/j.biopha.2017.12.078. Epub 2017 Dec 27.
• [39] Protein kinase CK2 catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-B signaling pathway.Biochem Pharmacol. 2017 May 15;132:102-117. doi: 10.1016/j.bcp.2017.02.016. Epub 2017 Feb 23.
• [40] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [41] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
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• [44] 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.
• [45] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [46] 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.
• [47] 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.
• [48] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.