Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8S67QS)

• DOT Name: Cyclin-dependent kinase 15 (CDK15)
• Synonyms: EC 2.7.11.22; Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 7 protein; Cell division protein kinase 15; Serine/threonine-protein kinase ALS2CR7; Serine/threonine-protein kinase PFTAIRE-2
• Gene Name: CDK15
• Related Disease:
  B-cell neoplasm
  Melanoma
  Thyroid gland papillary carcinoma
  Advanced cancer
  Bladder cancer
  Breast neoplasm
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  Tuberculosis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Ductal breast carcinoma in situ
  Osteoarthritis
  Pancreatic cancer
  Breast cancer
  Breast carcinoma
  Cutaneous melanoma
  Pneumonia
• UniProt ID: CDK15_HUMAN
• EC Number: 2.7.11.22
• Pfam ID: PF00069
• Sequence:
  MGQELCAKTVQPGCSCYHCSEGGEAHSCRRSQPETTEAAFKLTDLKEASCSMTSFHPRGL
  QAARAQKFKSKRPRSNSDCFQEEDLRQGFQWRKSLPFGAASSYLNLEKLGEGSYATVYKG
  ISRINGQLVALKVISMNAEEGVPFTAIREASLLKGLKHANIVLLHDIIHTKETLTFVFEY
  MHTDLAQYMSQHPGGLHPHNVRLFMFQLLRGLAYIHHQHVLHRDLKPQNLLISHLGELKL
  ADFGLARAKSIPSQTYSSEVVTLWYRPPDALLGATEYSSELDIWGAGCIFIEMFQGQPLF
  PGVSNILEQLEKIWEVLGVPTEDTWPGVSKLPNYNPEWFPLPTPRSLHVVWNRLGRVPEA
  EDLASQMLKGFPRDRVSAQEALVHDYFSALPSQLYQLPDEESLFTVSGVRLKPEMCDLLA
  SYQKGHHPAQFSKCW
• Function: Serine/threonine-protein kinase that acts like an antiapoptotic protein that counters TRAIL/TNFSF10-induced apoptosis by inducing phosphorylation of BIRC5 at 'Thr-34'.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell neoplasm	DISVY326	Definitive	Altered Expression	[1]
Melanoma	DIS1RRCY	Definitive	Biomarker	[2]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[7]
Glioma	DIS5RPEH	Strong	Altered Expression	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[8]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[9]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[5]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Biomarker	[10]
Osteoarthritis	DIS05URM	moderate	Altered Expression	[11]
Pancreatic cancer	DISJC981	moderate	Biomarker	[12]
Breast cancer	DIS7DPX1	Disputed	Altered Expression	[13]
Breast carcinoma	DIS2UE88	Disputed	Altered Expression	[13]
Cutaneous melanoma	DIS3MMH9	Disputed	Biomarker	[2]
Pneumonia	DIS8EF3M	Limited	Genetic Variation	[14]

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 Cyclin-dependent kinase 15 (CDK15).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cyclin-dependent kinase 15 (CDK15).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cyclin-dependent kinase 15 (CDK15).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cyclin-dependent kinase 15 (CDK15).	[16]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Cyclin-dependent kinase 15 (CDK15).	[17]
Malathion	DMXZ84M	Approved	Malathion increases the expression of Cyclin-dependent kinase 15 (CDK15).	[18]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cyclin-dependent kinase 15 (CDK15).	[20]

References

• [1] Effects of propofol on proliferation and anti-apoptosis of neuroblastoma SH-SY5Y cell line: new insights into neuroprotection.Brain Res. 2011 Apr 12;1384:42-50. doi: 10.1016/j.brainres.2011.02.004. Epub 2011 Feb 25.
• [2] Long-term Survival of Stage IV Melanoma Patients Treated with BOLD Combination Chemotherapy and Intermediate-dose Subcutaneous Interferon-alpha.Anticancer Res. 2018 Nov;38(11):6393-6397. doi: 10.21873/anticanres.12999.
• [3] Ang1/Tie2 induces cell proliferation and migration in human papillary thyroid carcinoma via the PI3K/AKT pathway.Oncol Lett. 2018 Jan;15(1):1313-1318. doi: 10.3892/ol.2017.7367. Epub 2017 Nov 8.
• [4] Single-Nucleotide Polymorphisms in TAOK3 Are Associated With High Opioid Requirement for Pain Management in Patients With Advanced Cancer Admitted to a Tertiary Palliative Care Unit.J Pain Symptom Manage. 2018 Oct;56(4):560-566. doi: 10.1016/j.jpainsymman.2018.07.011. Epub 2018 Jul 20.
• [5] Mutations in FGFR3 and PIK3CA, singly or combined with RAS and AKT1, are associated with AKT but not with MAPK pathway activation in urothelial bladder cancer.Hum Pathol. 2012 Oct;43(10):1573-82. doi: 10.1016/j.humpath.2011.10.026. Epub 2012 Mar 12.
• [6] PA28/ Promote Breast Cancer Cell Invasion and Metastasis via Down-Regulation of CDK15.Front Oncol. 2019 Nov 22;9:1283. doi: 10.3389/fonc.2019.01283. eCollection 2019.
• [7] High expression of PFTK1 in cancer cells predicts poor prognosis in colorectal cancer.Mol Med Rep. 2017 Jul;16(1):224-230. doi: 10.3892/mmr.2017.6560. Epub 2017 May 10.
• [8] Drug resistance to targeted therapeutic strategies in non-small cell lung cancer.Pharmacol Ther. 2020 Feb;206:107438. doi: 10.1016/j.pharmthera.2019.107438. Epub 2019 Nov 9.
• [9] Synthesis and antimycobacterial activity of imidazo[1,2-b][1,2,4,5]tetrazines.Eur J Med Chem. 2019 Sep 15;178:39-47. doi: 10.1016/j.ejmech.2019.05.081. Epub 2019 May 31.
• [10] Analysis of gene expression in ductal carcinoma in situ of the breast.Clin Cancer Res. 2002 Dec;8(12):3788-95.
• [11] Effect of silibinin on CFLAR-JNK pathway in oleic acid-treated HepG2 cells.Biomed Pharmacother. 2018 Dec;108:716-723. doi: 10.1016/j.biopha.2018.09.089. Epub 2018 Sep 21.
• [12] Primate-specific miRNA-637 inhibited tumorigenesis in human pancreatic ductal adenocarcinoma cells by suppressing Akt1 expression.Exp Cell Res. 2018 Feb 15;363(2):310-314. doi: 10.1016/j.yexcr.2018.01.026.
• [13] RNAi-mediated downregulation of CDKL1 inhibits growth and colony-formation ability, promotes apoptosis of human melanoma cells.J Dermatol Sci. 2015 Jul;79(1):57-63. doi: 10.1016/j.jdermsci.2015.03.020. Epub 2015 Apr 9.
• [14] Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies.J Exp Med. 2008 Jan 21;205(1):117-31. doi: 10.1084/jem.20071168. Epub 2007 Dec 31.
• [15] 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.
• [16] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [17] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [18] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [19] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [20] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [21] 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.