Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN9ZP68)

• DOT Name: Cyclin-dependent kinase 11B (CDK11B)
• Synonyms: EC 2.7.11.22; Cell division cycle 2-like protein kinase 1; CLK-1; Cell division protein kinase 11B; Galactosyltransferase-associated protein kinase p58/GTA; PITSLRE serine/threonine-protein kinase CDC2L1; p58 CLK-1
• Gene Name: CDK11B
• UniProt ID: CD11B_HUMAN
• PDB ID: 7UKZ
• EC Number: 2.7.11.22
• Pfam ID: PF00069
• Sequence:
  MGDEKDSWKVKTLDEILQEKKRRKEQEEKAEIKRLKNSDDRDSKRDSLEEGELRDHRMEI
  TIRNSPYRREDSMEDRGEEDDSLAIKPPQQMSRKEKAHHRKDEKRKEKRRHRSHSAEGGK
  HARVKEKEREHERRKRHREEQDKARREWERQKRREMAREHSRRERDRLEQLERKRERERK
  MREQQKEQREQKERERRAEERRKEREARREVSAHHRTMREDYSDKVKASHWSRSPPRPPR
  ERFELGDGRKPGEARPAPAQKPAQLKEEKMEERDLLSDLQDISDSERKTSSAESSSAESG
  SGSEEEEEEEEEEEEEGSTSEESEEEEEEEEEEEEETGSNSEEASEQSAEEVSEEEMSED
  EERENENHLLVVPESRFDRDSGESEEAEEEVGEGTPQSSALTEGDYVPDSPALSPIELKQ
  ELPKYLPALQGCRSVEEFQCLNRIEEGTYGVVYRAKDKKTDEIVALKRLKMEKEKEGFPI
  TSLREINTILKAQHPNIVTVREIVVGSNMDKIYIVMNYVEHDLKSLMETMKQPFLPGEVK
  TLMIQLLRGVKHLHDNWILHRDLKTSNLLLSHAGILKVGDFGLAREYGSPLKAYTPVVVT
  LWYRAPELLLGAKEYSTAVDMWSVGCIFGELLTQKPLFPGKSEIDQINKVFKDLGTPSEK
  IWPGYSELPAVKKMTFSEHPYNNLRKRFGALLSDQGFDLMNKFLTYFPGRRISAEDGLKH
  EYFRETPLPIDPSMFPTWPAKSEQQRVKRGTSPRPPEGGLGYSQLGDDDLKETGFHLTTT
  NQGASAAGPGFSLKF
• Function: Plays multiple roles in cell cycle progression, cytokinesis and apoptosis. Involved in pre-mRNA splicing in a kinase activity-dependent manner. Isoform 7 may act as a negative regulator of normal cell cycle progression.
• Tissue Specificity: Expressed ubiquitously. Some evidence of isoform-specific tissue distribution.
• Reactome Pathway: Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Cyclin-dependent kinase 11B (CDK11B).	[1]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Cyclin-dependent kinase 11B (CDK11B).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cyclin-dependent kinase 11B (CDK11B).	[7]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Cyclin-dependent kinase 11B (CDK11B).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Cyclin-dependent kinase 11B (CDK11B).	[5]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Cyclin-dependent kinase 11B (CDK11B).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cyclin-dependent kinase 11B (CDK11B).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cyclin-dependent kinase 11B (CDK11B).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cyclin-dependent kinase 11B (CDK11B).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cyclin-dependent kinase 11B (CDK11B).	[6]

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] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] 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.
• [6] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [7] 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.
• [8] 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.