Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUZI597)

• DOT Name: RING finger protein 24 (RNF24)
• Gene Name: RNF24
• Related Disease: Barrett esophagus
• UniProt ID: RNF24_HUMAN
• PDB ID: 2EP4
• Pfam ID: PF13639
• Sequence:
  MSSDFPHYNFRMPNIGFQNLPLNIYIVVFGTAIFVFILSLLFCCYLIRLRHQAHKEFYAY
  KQVILKEKVKELNLHELCAVCLEDFKPRDELGICPCKHAFHRKCLIKWLEVRKVCPLCNM
  PVLQLAQLHSKQDRGPPQGPLPGAENIV
• Function: May play a role in TRPCs intracellular trafficking.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Barrett esophagus	DIS416Y7	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of RING finger protein 24 (RNF24).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RING finger protein 24 (RNF24).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RING finger protein 24 (RNF24).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RING finger protein 24 (RNF24).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RING finger protein 24 (RNF24).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RING finger protein 24 (RNF24).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of RING finger protein 24 (RNF24).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of RING finger protein 24 (RNF24).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of RING finger protein 24 (RNF24).	[10]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of RING finger protein 24 (RNF24).	[10]
2-deoxyglucose	DMIAHVU	Approved	2-deoxyglucose decreases the expression of RING finger protein 24 (RNF24).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RING finger protein 24 (RNF24).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of RING finger protein 24 (RNF24).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RING finger protein 24 (RNF24).	[13]
Scriptaid	DM9JZ21	Preclinical	Scriptaid increases the expression of RING finger protein 24 (RNF24).	[10]
Oxamflatin	DM1TG3C	Terminated	Oxamflatin increases the expression of RING finger protein 24 (RNF24).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of RING finger protein 24 (RNF24).	[15]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of RING finger protein 24 (RNF24).	[10]
Apicidin	DM83WVF	Investigative	Apicidin increases the expression of RING finger protein 24 (RNF24).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RING finger protein 24 (RNF24).	[14]

References

• [1] RING finger proteins are involved in the progression of barrett esophagus to esophageal adenocarcinoma: a preliminary study.Gut Liver. 2014 Sep;8(5):487-94. doi: 10.5009/gnl13133. Epub 2014 Feb 24.
• [2] 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.
• [3] 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.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [10] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] 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.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.