Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAV67EJ)

• DOT Name: CLOCK-interacting pacemaker (CIPC)
• Synonyms: CLOCK-interacting circadian protein
• Gene Name: CIPC
• UniProt ID: CIPC_HUMAN
• Pfam ID: PF15800
• Sequence:
  MERKNPSRESPRRLSAKVGKGTEMKKVARQLGMAAAESDKDSGFSDGSSECLSSAEQMES
  EDMLSALGWSREDRPRQNSKTAKNAFPTLSPMVVMKNVLVKQGSSSSQLQSWTVQPSFEV
  ISAQPQLLFLHPPVPSPVSPCHTGEKKSDSRNYLPILNSYTKIAPHPGKRGLSLGPEEKG
  TSGVQKKICTERLGPSLSSSEPTKAGAVPSSPSTPAPPSAKLAEDSALQGVPSLVAGGSP
  QTLQPVSSSHVAKAPSLTFASPASPVCASDSTLHGLESNSPLSPLSANYSSPLWAAEHLC
  RSPDIFSEQRQSKHRRFQNTLVVLHKSGLLEITLKTKELIRQNQATQVELDQLKEQTQLF
  IEATKSRAPQAWAKLQASLTPGSSNTGSDLEAFSDHPAI
• Function: Transcriptional repressor which may act as a negative-feedback regulator of CLOCK-BMAL1 transcriptional activity in the circadian-clock mechanism. May stimulate BMAL1-dependent phosphorylation of CLOCK. However, the physiological relevance of these observations is unsure, since experiments in an animal model showed that CIPC is not critially required for basic circadian clock.

Molecular Interaction Atlas (MIA) of This DOT

10 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 CLOCK-interacting pacemaker (CIPC).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of CLOCK-interacting pacemaker (CIPC).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of CLOCK-interacting pacemaker (CIPC).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of CLOCK-interacting pacemaker (CIPC).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of CLOCK-interacting pacemaker (CIPC).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of CLOCK-interacting pacemaker (CIPC).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of CLOCK-interacting pacemaker (CIPC).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of CLOCK-interacting pacemaker (CIPC).	[1]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of CLOCK-interacting pacemaker (CIPC).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of CLOCK-interacting pacemaker (CIPC).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of CLOCK-interacting pacemaker (CIPC).	[6]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [7] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [8] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.