Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8ZPQLC)

• DOT Name: RUN domain-containing protein 3B (RUNDC3B)
• Synonyms: Rap2-binding protein 9; Rap2-interacting protein 9; RPIP-9
• Gene Name: RUNDC3B
• Related Disease:
  Advanced cancer
  Breast carcinoma
  Lung carcinoma
  Neoplasm
  Schizophrenia
• UniProt ID: RUN3B_HUMAN
• Pfam ID: PF02759
• Sequence:
  MASRSLGGLSGIRGGGGGGGKKSLSARNAAVERRNLITVCRFSVKTLIDRSCFETIDDSS
  PEFNNFAAILEQILSHRLKEISQSCRWLAHLQIPLQGQVTWFGYESPRSFWDYIRVACRK
  VSQNCICSIENMENVSSSRAKGRAWIRVALMEKHLSEYISTALRDFKTTRRFYEDGAIVL
  GEEANMLAGMLLGLNAIDFSFCLKGEGLDGSFPAVIDYTPYLKYIQSSDSISSDEEELRT
  LGSSGSESSTPENVGPPFLMDENSWFNKCKRVKQKYQLTLEQKGYLEELLRLRENQLSES
  VSQNKILLQRIEDSDLAHKLEKEQLEYIIVELQDQLTVLKNNDLRSRQELTAHLTNQWPS
  PGALDVNAVALDTLLYRKHNKQWYEKSYQSLDQLSAEVSLSQTSLDPGQSQEGDGKQDTL
  NVMSEGKEDTPSLLGLCGSLTSVASYKSLTSLKSNDYLASPTTEMTSPGLTPS
• Tissue Specificity: Isoform 2 is expressed at high levels in brain, thymus, ovary, testis, leukocyte, liver, small intestine and prostate. Isoform 1 is expressed in the brain, testis and adrenal gland. It is activated in tumorigenic breast cancer cell lines and in the primary tumor of breast cancer patients. Activation also correlates with metastatic lymph node invasion and can be detected in metastatic epithelial cells from the lymph nodes and in the bone marrow of patients.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[3]
Schizophrenia	DISSRV2N	No Known	Unknown	[4]

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 RUN domain-containing protein 3B (RUNDC3B).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RUN domain-containing protein 3B (RUNDC3B).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RUN domain-containing protein 3B (RUNDC3B).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of RUN domain-containing protein 3B (RUNDC3B).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RUN domain-containing protein 3B (RUNDC3B).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of RUN domain-containing protein 3B (RUNDC3B).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of RUN domain-containing protein 3B (RUNDC3B).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of RUN domain-containing protein 3B (RUNDC3B).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of RUN domain-containing protein 3B (RUNDC3B).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of RUN domain-containing protein 3B (RUNDC3B).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of RUN domain-containing protein 3B (RUNDC3B).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of RUN domain-containing protein 3B (RUNDC3B).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of RUN domain-containing protein 3B (RUNDC3B).	[20]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RUN domain-containing protein 3B (RUNDC3B).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of RUN domain-containing protein 3B (RUNDC3B).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of RUN domain-containing protein 3B (RUNDC3B).	[19]

References

• [1] The expression of RUNDC3B is associated with promoter methylation in lymphoid malignancies.Hematol Oncol. 2017 Mar;35(1):25-33. doi: 10.1002/hon.2238. Epub 2015 May 25.
• [2] Expression of RPIP9 (Rap2 interacting protein 9) is activated in breast carcinoma and correlates with a poor prognosis.Int J Cancer. 2005 Dec 20;117(6):934-41. doi: 10.1002/ijc.21252.
• [3] Large-scale CpG methylation analysis identifies novel candidate genes and reveals methylation hotspots in acute lymphoblastic leukemia. Cancer Res. 2007 Mar 15;67(6):2617-25.
• [4] De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014 Feb 13;506(7487):179-84. doi: 10.1038/nature12929. Epub 2014 Jan 22.
• [5] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.