Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8863O1)

• DOT Name: Cyclin-I (CCNI)
• Gene Name: CCNI
• Related Disease:
  Malaria
  Cervical cancer
  Cervical carcinoma
  Epithelial ovarian cancer
  Neoplasm
• UniProt ID: CCNI_HUMAN
• Pfam ID: PF00134
• Sequence:
  MKFPGPLENQRLSFLLEKAITREAQMWKVNVRKMPSNQNVSPSQRDEVIQWLAKLKYQFN
  LYPETFALASSLLDRFLATVKAHPKYLSCIAISCFFLAAKTVEEDERIPVLKVLARDSFC
  GCSSSEILRMERIILDKLNWDLHTATPLDFLHIFHAIAVSTRPQLLFSLPKLSPSQHLAV
  LTKQLLHCMACNQLLQFRGSMLALAMVSLEMEKLIPDWLSLTIELLQKAQMDSSQLIHCR
  ELVAHHLSTLQSSLPLNSVYVYRPLKHTLVTCDKGVFRLHPSSVPGPDFSKDNSKPEVPV
  RGTAAFYHHLPAASGCKQTSTKRKVEEMEVDDFYDGIKRLYNEDNVSENVGSVCGTDLSR
  QEGHASPCPPLQPVSVM
• Tissue Specificity: Highest levels in adult heart, brain and skeletal muscle. Lower levels in adult placenta, lung, kidney and pancreas. Also high levels in fetal brain and lower levels in fetal lung, liver and kidney. Also abundant in testis and thyroid.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malaria	DISQ9Y50	Definitive	Biomarker	[1]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]

1 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-I (CCNI).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cyclin-I (CCNI).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cyclin-I (CCNI).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclin-I (CCNI).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Cyclin-I (CCNI).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cyclin-I (CCNI).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cyclin-I (CCNI).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cyclin-I (CCNI).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cyclin-I (CCNI).	[12]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Cyclin-I (CCNI).	[13]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of Cyclin-I (CCNI).	[14]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Cyclin-I (CCNI).	[15]

References

• [1] The Malaria Parasite Cyclin H Homolog PfCyc1 Is Required for Efficient Cytokinesis in Blood-Stage Plasmodium falciparum.mBio. 2017 Jun 13;8(3):e00605-17. doi: 10.1128/mBio.00605-17.
• [2] Cyclin I promotes cisplatin resistance via Cdk5 activation in cervical cancer.Eur Rev Med Pharmacol Sci. 2015 Dec;19(23):4533-41.
• [3] Cyclin I mRNA expression correlates with kinase insert domain receptor expression in human epithelial ovarian cancer.Anticancer Res. 2015 Feb;35(2):1115-9.
• [4] 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.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] 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.
• [8] Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
• [9] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [10] 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.
• [11] 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.
• [12] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [13] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [14] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [15] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.