Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOLNN68)

• DOT Name: Cyclin-dependent kinase 20 (CDK20)
• Synonyms: EC 2.7.11.22; CDK-activating kinase p42; CAK-kinase p42; Cell cycle-related kinase; Cell division protein kinase 20; Cyclin-dependent protein kinase H; Cyclin-kinase-activating kinase p42
• Gene Name: CDK20
• Related Disease:
  Acute myelogenous leukaemia
  Adult glioblastoma
  Alcohol dependence
  Alcohol use disorder
  Carcinoma
  Chronic kidney disease
  Glioblastoma multiforme
  Promyelocytic leukaemia
  Hepatocellular carcinoma
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Brain infarction
  Complex neurodevelopmental disorder
  Lung cancer
  Lung carcinoma
• UniProt ID: CDK20_HUMAN
• EC Number: 2.7.11.22
• Pfam ID: PF00069
• Sequence:
  MDQYCILGRIGEGAHGIVFKAKHVETGEIVALKKVALRRLEDGFPNQALREIKALQEMED
  NQYVVQLKAVFPHGGGFVLAFEFMLSDLAEVVRHAQRPLAQAQVKSYLQMLLKGVAFCHA
  NNIVHRDLKPANLLISASGQLKIADFGLARVFSPDGSRLYTHQVATRWYRAPELLYGARQ
  YDQGVDLWSVGCIMGELLNGSPLFPGKNDIEQLCYVLRILGTPNPQVWPELTELPDYNKI
  SFKEQVPMPLEEVLPDVSPQALDLLGQFLLYPPHQRIAASKALLHQYFFTAPLPAHPSEL
  PIPQRLGGPAPKAHPGPPHIHDFHVDRPLEESLLNPELIRPFILEG
• Function: Required for high-level Shh responses in the developing neural tube. Together with TBC1D32, controls the structure of the primary cilium by coordinating assembly of the ciliary membrane and axoneme, allowing GLI2 to be properly activated in response to SHH signaling. Involved in cell growth. Activates CDK2, a kinase involved in the control of the cell cycle, by phosphorylating residue 'Thr-160'.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[2]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[3]
Alcohol use disorder	DISMB65Y	Strong	Biomarker	[3]
Carcinoma	DISH9F1N	Strong	Altered Expression	[4]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[5]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[2]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[7]
Prostate cancer	DISF190Y	moderate	Biomarker	[8]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[8]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[9]
Brain infarction	DISPPGYK	Limited	Genetic Variation	[10]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[11]
Lung cancer	DISCM4YA	Limited	Biomarker	[9]
Lung carcinoma	DISTR26C	Limited	Biomarker	[9]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Cyclin-dependent kinase 20 (CDK20) affects the response to substance of Ethanol.	[3]

6 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 Cyclin-dependent kinase 20 (CDK20).	[12]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclin-dependent kinase 20 (CDK20).	[13]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Cyclin-dependent kinase 20 (CDK20).	[14]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Cyclin-dependent kinase 20 (CDK20).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cyclin-dependent kinase 20 (CDK20).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cyclin-dependent kinase 20 (CDK20).	[17]

References

• [1] The presence of C/EBP and its degradation are both required for TRIB2-mediated leukaemia.Oncogene. 2016 Oct 6;35(40):5272-5281. doi: 10.1038/onc.2016.66. Epub 2016 Mar 21.
• [2] EBP1 protein modulates the expression of human MHC class II molecules in non-hematopoietic cancer cells.Int J Oncol. 2015 Aug;47(2):481-9. doi: 10.3892/ijo.2015.3051. Epub 2015 Jun 16.
• [3] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
• [4] Overexpression of the Ets-1 transcription factor in human breast cancer.Br J Cancer. 2004 Oct 4;91(7):1308-15. doi: 10.1038/sj.bjc.6602128.
• [5] Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment. Nat Commun. 2018 May 17;9(1):1960. doi: 10.1038/s41467-018-04193-w.
• [6] Restoration of CCAAT enhancer binding protein P42 induces myeloid differentiation and overcomes all-trans retinoic acid resistance in human acute promyelocytic leukemia NB4-R1 cells.Int J Oncol. 2015 Nov;47(5):1685-95. doi: 10.3892/ijo.2015.3163. Epub 2015 Sep 14.
• [7] YC-1 Antagonizes Wnt/-Catenin Signaling Through the EBP1 p42 Isoform in Hepatocellular Carcinoma.Cancers (Basel). 2019 May 13;11(5):661. doi: 10.3390/cancers11050661.
• [8] Novel identification of the ETS-1 splice variants p42 and p27 in prostate cancer cell lines.Oncol Rep. 2012 May;27(5):1321-4. doi: 10.3892/or.2012.1667. Epub 2012 Feb 1.
• [9] CDK20 interacts with KEAP1 to activate NRF2 and promotes radiochemoresistance in lung cancer cells.Oncogene. 2017 Sep 14;36(37):5321-5330. doi: 10.1038/onc.2017.161. Epub 2017 May 22.
• [10] Thrombin Preconditioning Enhances Therapeutic Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells in Severe Neonatal Hypoxic Ischemic Encephalopathy.Int J Mol Sci. 2019 May 20;20(10):2477. doi: 10.3390/ijms20102477.
• [11] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [12] 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.
• [13] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [14] Marked regression of liver metastasis by combined therapy of ultrasound-mediated NF kappaB-decoy transfer and transportal injection of paclitaxel, in mouse. Int J Cancer. 2008 Apr 1;122(7):1645-56. doi: 10.1002/ijc.23280.
• [15] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [18] Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.