Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO35W64)

• DOT Name: Cyclin-dependent kinase 17 (CDK17)
• Synonyms: EC 2.7.11.22; Cell division protein kinase 17; PCTAIRE-motif protein kinase 2; Serine/threonine-protein kinase PCTAIRE-2
• Gene Name: CDK17
• UniProt ID: CDK17_HUMAN
• EC Number: 2.7.11.22
• Pfam ID: PF12330 ; PF00069
• Sequence:
  MKKFKRRLSLTLRGSQTIDESLSELAEQMTIEENSSKDNEPIVKNGRPPTSHSMHSFLHQ
  YTGSFKKPPLRRPHSVIGGSLGSFMAMPRNGSRLDIVHENLKMGSDGESDQASGTSSDEV
  QSPTGVCLRNRIHRRISMEDLNKRLSLPADIRIPDGYLEKLQINSPPFDQPMSRRSRRAS
  LSEIGFGKMETYIKLEKLGEGTYATVYKGRSKLTENLVALKEIRLEHEEGAPCTAIREVS
  LLKDLKHANIVTLHDIVHTDKSLTLVFEYLDKDLKQYMDDCGNIMSMHNVKLFLYQILRG
  LAYCHRRKVLHRDLKPQNLLINEKGELKLADFGLARAKSVPTKTYSNEVVTLWYRPPDVL
  LGSSEYSTQIDMWGVGCIFFEMASGRPLFPGSTVEDELHLIFRLLGTPSQETWPGISSNE
  EFKNYNFPKYKPQPLINHAPRLDSEGIELITKFLQYESKKRVSAEEAMKHVYFRSLGPRI
  HALPESVSIFSLKEIQLQKDPGFRNSSYPETGHGKNRRQSMLF
• Function: May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Cyclin-dependent kinase 17 (CDK17).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cyclin-dependent kinase 17 (CDK17).	[2]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cyclin-dependent kinase 17 (CDK17).	[3]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Cyclin-dependent kinase 17 (CDK17).	[4]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cyclin-dependent kinase 17 (CDK17).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cyclin-dependent kinase 17 (CDK17).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cyclin-dependent kinase 17 (CDK17).	[7]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [4] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [5] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] 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.