Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSL5ZFF)

• DOT Name: Cyclin-Y-like protein 1 (CCNYL1)
• Gene Name: CCNYL1
• UniProt ID: CCYL1_HUMAN
• Pfam ID: PF00134
• Sequence:
  MGNTLTCCVSPNASPKLGRRAGSAELYCASDIYEAVSGDAVAVAPAVVEPAELDFGEGEG
  HHLQHISDREMPEDLALESNPSDHPRASTIFLSKSQTDVREKRKSNHLNHVSPGQLTKKY
  SSCSTIFLDDSTVSQPNLRTTVKCVTLAIYYHIKNRDANRSLDIFDERSHPLTREKVPEE
  YFKHDPEHKFIYRFVRTLFSAAQLTAECAIVTLVYLERLLTYAEIDICPTNWKRIVLGAI
  LLASKVWDDQAVWNVDYCQILKDITVEDMNEMERHFLELLQFNINVPASVYAKYYFDLRS
  LADDNNLNFLFAPLSKERAQNLEAISRLCEDKDLCRAAMRRSFSADNFIGIQRSKAILS
• Function: Key regulator of Wnt signaling implicated in various biological processes including male fertility, embryonic neurogenesis and cortex development. Activates the cyclin-dependent kinase CDK16, and promotes sperm maturation.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cyclin-Y-like protein 1 (CCNYL1).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cyclin-Y-like protein 1 (CCNYL1).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[13]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Cyclin-Y-like protein 1 (CCNYL1).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Cyclin-Y-like protein 1 (CCNYL1).	[11]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] 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.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [11] 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.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.