Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT183N7L)

• DOT Name: Cyclin-Q (CCNQ)
• Synonyms: CDK10-activating cyclin; Cyclin-M; Cyclin-related protein FAM58A
• Gene Name: CCNQ
• Related Disease:
  Syndactyly-telecanthus-anogenital and renal malformations syndrome
  Advanced cancer
  Gallbladder cancer
  Non-insulin dependent diabetes
  Familial primary hypomagnesemia
  High blood pressure
• UniProt ID: CCNQ_HUMAN
• Pfam ID: PF00134
• Sequence:
  MEAPEGGGGGPAARGPEGQPAPEARVHFRVARFIMEAGVKLGMRSIPIATACTIYHKFFC
  ETNLDAYDPYLIAMSSIYLAGKVEEQHLRTRDIINVSNRYFNPSGEPLELDSRFWELRDS
  IVQCELLMLRVLRFQVSFQHPHKYLLHYLVSLQNWLNRHSWQRTPVAVTAWALLRDSYHG
  ALCLRFQAQHIAVAVLYLALQVYGVEVPAEVEAEKPWWQVFNDDLTKPIIDNIVSDLIQI
  YTMDTEIP
• Function: Activating cyclin for the cyclin-associated kinase CDK10.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Syndactyly-telecanthus-anogenital and renal malformations syndrome	DISZA8BN	Definitive	X-linked	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Gallbladder cancer	DISXJUAF	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[4]
Familial primary hypomagnesemia	DIS6TTKI	moderate	Genetic Variation	[2]
High blood pressure	DISY2OHH	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cyclin-Q (CCNQ).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cyclin-Q (CCNQ).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cyclin-Q (CCNQ).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cyclin-Q (CCNQ).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cyclin-Q (CCNQ).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cyclin-Q (CCNQ).	[10]

References

• [1] An autosomal dominant syndrome of renal and anogenital malformations with syndactyly. J Med Genet. 1996 Jul;33(7):594-6. doi: 10.1136/jmg.33.7.594.
• [2] Molecular function and biological importance of CNNM family Mg2+ transporters.J Biochem. 2019 Mar 1;165(3):219-225. doi: 10.1093/jb/mvy095.
• [3] miR-433 accelerates acquired chemoresistance of gallbladder cancer cells by targeting cyclin M.Oncol Lett. 2018 Mar;15(3):3305-3312. doi: 10.3892/ol.2017.7708. Epub 2017 Dec 28.
• [4] A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.Diabetes. 2013 Jan;62(1):291-8. doi: 10.2337/db12-0454. Epub 2012 Sep 6.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] 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.