Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHN25MF)

• DOT Name: U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3)
• Synonyms: U3 snoRNP protein IMP3; BRMS2
• Gene Name: IMP3
• UniProt ID: IMP3_HUMAN
• PDB ID: 2CQJ; 7MQ8; 7MQ9; 7MQA
• Pfam ID: PF00163 ; PF01479
• Sequence:
  MVRKLKFHEQKLLKQVDFLNWEVTDHNLHELRVLRRYRLQRREDYTRYNQLSRAVRELAR
  RLRDLPERDQFRVRASAALLDKLYALGLVPTRGSLELCDFVTASSFCRRRLPTVLLKLRM
  AQHLQAAVAFVEQGHVRVGPDVVTDPAFLVTRSMEDFVTWVDSSKIKRHVLEYNEERDDF
  DLEA
• Function: Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
• KEGG Pathway: Ribosome biogenesis in eukaryotes (hsa03008)
• Reactome Pathway:
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

17 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 U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[8]
Marinol	DM70IK5	Approved	Marinol increases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[16]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of U3 small nucleolar ribonucleoprotein protein IMP3 (IMP3).	[17]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [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] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [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] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [17] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.