Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0S9MFX)

• DOT Name: LON peptidase N-terminal domain and RING finger protein 1 (LONRF1)
• Synonyms: RING finger protein 191
• Gene Name: LONRF1
• UniProt ID: LONF1_HUMAN
• Pfam ID: PF02190 ; PF00097 ; PF13923
• Sequence:
  MSSPAVARTSPGGSREMAPAPQGRGRFWEVGGGSGHRLERAAAESERWELLLRRGELLAL
  GGHLKGALEAFAAALRRGAPARPECLGALVDCLVFNYRLRHGLGWSAAPVAGADGGAGGL
  LRCLGCRGFLSEPVTVPCGHSYCRRCLRRELRARCRLCRDRLPPATASATDAEGTAPRPP
  PLAAAIAASDFRTSVVLNHLAEKWFPGQRERARAAGRLGELLHQGRYREALAAACEALRA
  EPSDLIVKIYRAESYAGLQEFKAAIEDLNAVLFQLPDWPEVYFRKGKVLCDAGFLGDALQ
  LFLQCLALDEDFAPAKLQVQKILCDLLLPENLKEGLKESSWSSLPCTKNRPFDFHSVMEE
  SQSLNEPSPKQSEEIPEVTSEPVKGSLNRAQSAQSINSTEMPAREDCLKRVSSEPVLSVQ
  EKGVLLKRKLSLLEQDVIVNEDGRNKLKKQGETPNEVCMFSLAYGDIPEELIDVSDFECS
  LCMRLFFEPVTTPCGHSFCKNCLERCLDHAPYCPLCKESLKEYLADRRYCVTQLLEELIV
  KYLPDELSERKKIYDEETAELSHLTKNVPIFVCTMAYPTVPCPLHVFEPRYRLMIRRSIQ
  TGTKQFGMCVSDTQNSFADYGCMLQIRNVHFLPDGRSVVDTVGGKRFRVLKRGMKDGYCT
  ADIEYLEDVKVENEDEIKNLRELHDLVYSQACSWFQNLRDRFRSQILQHFGSMPEREENL
  QAAPNGPAWCWWLLAVLPVDPRYQLSVLSMKSLKERLTKIQHILTYFSRDQSK
• Reactome Pathway: Antigen processing (R-HSA-983168)

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 decreases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[5]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[6]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[8]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[14]

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 increases the methylation of LON peptidase N-terminal domain and RING finger protein 1 (LONRF1).	[13]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] 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.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [7] Screening autism-associated environmental factors in differentiating human neural progenitors with fractional factorial design-based transcriptomics. Sci Rep. 2023 Jun 29;13(1):10519. doi: 10.1038/s41598-023-37488-0.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.