Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPUZ8CW)

• DOT Name: RNA-binding protein MEX3B (MEX3B)
• Synonyms: RING finger and KH domain-containing protein 3; RING finger protein 195
• Gene Name: MEX3B
• Related Disease:
  Advanced cancer
  Allergic asthma
• UniProt ID: MEX3B_HUMAN
• Pfam ID: PF00013 ; PF13920
• Sequence:
  MPSSLFADLERNGSGGGGGGSSGGGETLDDQRALQLALDQLSLLGLDSDEGASLYDSEPR
  KKSVNMTECVPVPSSEHVAEIVGRQGCKIKALRAKTNTYIKTPVRGEEPVFVVTGRKEDV
  AMARREIISAAEHFSMIRASRNKNTALNGAVPGPPNLPGQTTIQVRVPYRVVGLVVGPKG
  ATIKRIQQQTHTYIVTPSRDKEPVFEVTGMPENVDRAREEIEAHIALRTGGIIELTDEND
  FHANGTDVGFDLHHGSGGSGPGSLWSKPTPSITPTPGRKPFSSYRNDSSSSLGSASTDSY
  FGGGTSSSAAATQRLADYSPPSPALSFAHNGNNNNNGNGYTYTAGGEASVPSPDGCPELQ
  PTFDPAPAPPPGAPLIWAQFERSPGGGPAAPVSSSCSSSASSSASSSSVVFPGGGASAPS
  NANLGLLVHRRLHPGTSCPRLSPPLHMAPGAGEHHLARRVRSDPGGGGLAYAAYANGLGA
  QLPGLQPSDTSGSSSSSSSSSSSSSSSSGLRRKGSRDCSVCFESEVIAALVPCGHNLFCM
  ECANRICEKSEPECPVCHTAVTQAIRIFS
• Function: RNA-binding protein. May be involved in post-transcriptional regulatory mechanisms.
• Tissue Specificity: Highest levels found in fetal brain and testis. Detected in the adult intestinal epithelium, specifically in goblet cell at protein level.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Biomarker	[2]

18 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 RNA-binding protein MEX3B (MEX3B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RNA-binding protein MEX3B (MEX3B).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RNA-binding protein MEX3B (MEX3B).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA-binding protein MEX3B (MEX3B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of RNA-binding protein MEX3B (MEX3B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RNA-binding protein MEX3B (MEX3B).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of RNA-binding protein MEX3B (MEX3B).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RNA-binding protein MEX3B (MEX3B).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of RNA-binding protein MEX3B (MEX3B).	[11]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of RNA-binding protein MEX3B (MEX3B).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA-binding protein MEX3B (MEX3B).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of RNA-binding protein MEX3B (MEX3B).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of RNA-binding protein MEX3B (MEX3B).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of RNA-binding protein MEX3B (MEX3B).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of RNA-binding protein MEX3B (MEX3B).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of RNA-binding protein MEX3B (MEX3B).	[19]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of RNA-binding protein MEX3B (MEX3B).	[20]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of RNA-binding protein MEX3B (MEX3B).	[21]

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 RNA-binding protein MEX3B (MEX3B).	[17]

References

• [1] The RNA-binding Protein MEX3B Mediates Resistance to Cancer Immunotherapy by Downregulating HLA-A Expression.Clin Cancer Res. 2018 Jul 15;24(14):3366-3376. doi: 10.1158/1078-0432.CCR-17-2483. Epub 2018 Mar 1.
• [2] The RNA Binding Protein Mex-3B Is Required for IL-33 Induction in the Development of Allergic Airway Inflammation.Cell Rep. 2016 Aug 30;16(9):2456-71. doi: 10.1016/j.celrep.2016.07.062. Epub 2016 Aug 18.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [10] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [11] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [12] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] 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.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] 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.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [20] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [21] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.