Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1HK35I)

• DOT Name: Protein ripply3 (RIPPLY3)
• Synonyms: Down syndrome critical region protein 6
• Gene Name: RIPPLY3
• UniProt ID: DSCR6_HUMAN
• Pfam ID: PF14998
• Sequence:
  MEPEAAAGARKARGRGCHCPGDAPWRPPPPRGPESPAPWRPWIQTPGDAELTRTGRPLEP
  RADQHTFGSKGAFGFQHPVRVYLPMSKRQEYLRSSGEQVLASFPVQATIDFYDDESTESA
  SEAEEPEEGPPPLHLLPQEVGGRQENGPGGKGRDQGINQGQRSSGGGDHWGEGPLPQGVS
  SRGGKCSSSK
• Function: Acts as a transcriptional corepressor. Negative regulator of the transcriptional activity of TBX1. Plays a role in the development of the pharyngeal apparatus and derivatives.
• Tissue Specificity: Expressed at a low level in fetal kidney and fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

2 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 Protein ripply3 (RIPPLY3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein ripply3 (RIPPLY3).	[12]

15 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 Protein ripply3 (RIPPLY3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein ripply3 (RIPPLY3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein ripply3 (RIPPLY3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein ripply3 (RIPPLY3).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein ripply3 (RIPPLY3).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein ripply3 (RIPPLY3).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Protein ripply3 (RIPPLY3).	[8]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Protein ripply3 (RIPPLY3).	[9]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Protein ripply3 (RIPPLY3).	[9]
Dactinomycin	DM2YGNW	Approved	Dactinomycin increases the expression of Protein ripply3 (RIPPLY3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein ripply3 (RIPPLY3).	[10]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Protein ripply3 (RIPPLY3).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein ripply3 (RIPPLY3).	[11]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Protein ripply3 (RIPPLY3).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein ripply3 (RIPPLY3).	[13]

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] 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.
• [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] 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] 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.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [12] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [13] 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.