Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT95PP0W)

• DOT Name: LON peptidase N-terminal domain and RING finger protein 2 (LONRF2)
• Synonyms: Neuroblastoma apoptosis-related protease; RING finger protein 192
• Gene Name: LONRF2
• UniProt ID: LONF2_HUMAN
• Pfam ID: PF02190 ; PF13923
• Sequence:
  MSPEPVPPPPPPQCPGCDRAEPIAQRLEEGDEAFRAGDYEMAAELFRSMLAGLAQPDRGL
  CLRLGDALARAGRLPEALGAFRGAARLGALRPEELEELAGGLVRAVGLRDRPLSAENPGG
  EPEAPGEGGPAPEPRAPRDLLGCPRCRRLLHKPVTLPCGLTVCKRCVEPGPARPQVRRVN
  VVLSGLLEKCFPAECRLRRLAGQARSLQRQQQPEAALLRCDQALELAPDDNSLLLLRAEL
  YLTMKNYEQALQDASAACQNEPLLIKGHQVKAQALSGLGRSKEVLKEFLYCLALNPECNS
  VKKEAQKVMCEVLFSATANVHENLTSSIQSRLKAQGHSHMNAQALLEEGDAGSSENSSEK
  SDMLGNTNSSVLYFILGLHFEEDKKALESILPTAPSAGLKRQFPDDVEDAPDLNAPGKIP
  KKDLSLQRSPNSETEESQGLSLDVTDFECALCMRLLFEPVTTPCGHTFCLKCLERCLDHA
  PHCPLCKDKLSELLASRNFNITVLAEELIFRYLPDELSDRKRIYDEEMSELSNLTRDVPI
  FVCAMAFPTVPCPLHVFEPRYRLMIRRCMETGTKRFGMCLSAEHAGLSEYGCMLEIKDVR
  TFPDGSSVVDAIGISRFRVLSHRHRDGYNTADIEYLEDEKVEGPEYEELAALHDSVHQQS
  VSWFASLQDRMKEQILSHFGVMPDREPEPQSNPSGPAWSWWILAVLPLERKAQLAILGMT
  SLKERLLAIRRILVIITRKMNSRQELANARERNN

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 LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[10]

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 LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[9]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of LON peptidase N-terminal domain and RING finger protein 2 (LONRF2).	[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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] 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.
• [11] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [12] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [13] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.