Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAN4FSC)

• DOT Name: RNA-binding protein Musashi homolog 1 (MSI1)
• Synonyms: Musashi-1
• Gene Name: MSI1
• UniProt ID: MSI1H_HUMAN
• Pfam ID: PF00076
• Sequence:
  METDAPQPGLASPDSPHDPCKMFIGGLSWQTTQEGLREYFGQFGEVKECLVMRDPLTKRS
  RGFGFVTFMDQAGVDKVLAQSRHELDSKTIDPKVAFPRRAQPKMVTRTKKIFVGGLSVNT
  TVEDVKQYFEQFGKVDDAMLMFDKTTNRHRGFGFVTFESEDIVEKVCEIHFHEINNKMVE
  CKKAQPKEVMSPTGSARGRSRVMPYGMDAFMLGIGMLGYPGFQATTYASRSYTGLAPGYT
  YQFPEFRVERTPLPSAPVLPELTAIPLTAYGPMAAAAAAAAVVRGTGSHPWTMAPPPGST
  PSRTGGFLGTTSPGPMAELYGAANQDSGVSSYISAASPAPSTGFGHSLGGPLIATAFTNG
  YH
• Function: RNA binding protein that regulates the expression of target mRNAs at the translation level. Regulates expression of the NOTCH1 antagonist NUMB. Binds RNA containing the sequence 5'-GUUAGUUAGUUAGUU-3' and other sequences containing the pattern 5'-[GA]U(1-3)AGU-3'. May play a role in the proliferation and maintenance of stem cells in the central nervous system.
• Tissue Specificity: Detected in fetal kidney, brain, liver and lung, and in adult brain and pancreas. Detected in hepatoma cell lines.
• KEGG Pathway: mR. surveillance pathway (hsa03015)
• Reactome Pathway: Regulation of expression of SLITs and ROBOs (R-HSA-9010553)

Molecular Interaction Atlas (MIA) of This DOT

3 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 RNA-binding protein Musashi homolog 1 (MSI1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RNA-binding protein Musashi homolog 1 (MSI1).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RNA-binding protein Musashi homolog 1 (MSI1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin affects the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[6]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[7]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[2]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[9]
SB-431542	DM0YOXQ	Preclinical	SB-431542 affects the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[10]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[12]
Eckol	DMIVY0Q	Investigative	Eckol decreases the expression of RNA-binding protein Musashi homolog 1 (MSI1).	[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] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1. Mol Neurobiol. 2017 Jul;54(5):3798-3812. doi: 10.1007/s12035-016-9898-y. Epub 2016 Jun 7.
• [5] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [6] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [7] Resveratrol promotes proteasome-dependent degradation of Nanog via p53 activation and induces differentiation of glioma stem cells. Stem Cell Res. 2013 Jul;11(1):601-10. doi: 10.1016/j.scr.2013.04.004. Epub 2013 Apr 11.
• [8] 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.
• [9] 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.
• [10] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [11] 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.
• [12] Lithium chloride regulates the proliferation of stem-like cells in retinoblastoma cell lines: a potential role for the canonical Wnt signaling pathway. Mol Vis. 2010 Jan 13;16:36-45.
• [13] Eckol suppresses maintenance of stemness and malignancies in glioma stem-like cells. Toxicol Appl Pharmacol. 2011 Jul 1;254(1):32-40. doi: 10.1016/j.taap.2011.04.006. Epub 2011 Apr 14.