Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZA4SXL)

• DOT Name: Ras-related protein Rab-3B (RAB3B)
• Gene Name: RAB3B
• Related Disease:
  Glioma
  Prostate cancer
  Prostate carcinoma
  Parkinson disease
• UniProt ID: RAB3B_HUMAN
• PDB ID: 3DZ8; 8A4B; 8A4C
• Pfam ID: PF00071
• Sequence:
  MASVTDGKTGVKDASDQNFDYMFKLLIIGNSSVGKTSFLFRYADDTFTPAFVSTVGIDFK
  VKTVYRHEKRVKLQIWDTAGQERYRTITTAYYRGAMGFILMYDITNEESFNAVQDWATQI
  KTYSWDNAQVILVGNKCDMEEERVVPTEKGQLLAEQLGFDFFEASAKENISVRQAFERLV
  DAICDKMSDSLDTDPSMLGSSKNTRLSDTPPLLQQNCSC
• Function: Protein transport. Probably involved in vesicular traffic.
• Reactome Pathway: RAB geranylgeranylation (R-HSA-8873719)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	moderate	Biomarker	[2]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[2]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[3]

21 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 Ras-related protein Rab-3B (RAB3B).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Ras-related protein Rab-3B (RAB3B).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-3B (RAB3B).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Ras-related protein Rab-3B (RAB3B).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Ras-related protein Rab-3B (RAB3B).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ras-related protein Rab-3B (RAB3B).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Ras-related protein Rab-3B (RAB3B).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Ras-related protein Rab-3B (RAB3B).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Ras-related protein Rab-3B (RAB3B).	[12]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Ras-related protein Rab-3B (RAB3B).	[13]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Ras-related protein Rab-3B (RAB3B).	[14]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Ras-related protein Rab-3B (RAB3B).	[15]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Ras-related protein Rab-3B (RAB3B).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Ras-related protein Rab-3B (RAB3B).	[17]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ras-related protein Rab-3B (RAB3B).	[18]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Ras-related protein Rab-3B (RAB3B).	[20]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Ras-related protein Rab-3B (RAB3B).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ras-related protein Rab-3B (RAB3B).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ras-related protein Rab-3B (RAB3B).	[23]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Ras-related protein Rab-3B (RAB3B).	[24]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Ras-related protein Rab-3B (RAB3B).	[25]

1 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 Ras-related protein Rab-3B (RAB3B).	[19]

References

• [1] miR-200b as a prognostic factor targets multiple members of RAB family in glioma.Med Oncol. 2014 Mar;31(3):859. doi: 10.1007/s12032-014-0859-x. Epub 2014 Jan 30.
• [2] Integration of regulatory networks by NKX3-1 promotes androgen-dependent prostate cancer survival.Mol Cell Biol. 2012 Jan;32(2):399-414. doi: 10.1128/MCB.05958-11. Epub 2011 Nov 14.
• [3] Functional enhancement and protection of dopaminergic terminals by RAB3B overexpression.Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22474-9. doi: 10.1073/pnas.0912193106. Epub 2009 Dec 10.
• [4] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [5] 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.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [14] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [15] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [16] Thyroid hormone responsive genes in cultured human fibroblasts. J Clin Endocrinol Metab. 2005 Feb;90(2):936-43.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] 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.
• [19] 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.
• [20] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [21] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [22] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [23] 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.
• [24] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [25] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.