Details of Drug Off-Target (DOT)

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

• DOT Name: ADP-ribosylation factor-like protein 5B (ARL5B)
• Synonyms: ADP-ribosylation factor-like protein 8
• Gene Name: ARL5B
• Related Disease:
  Major depressive disorder
  Urolithiasis
  Melanoma
• UniProt ID: ARL5B_HUMAN
• PDB ID: 1YZG
• Pfam ID: PF00025
• Sequence:
  MGLIFAKLWSLFCNQEHKVIIVGLDNAGKTTILYQFLMNEVVHTSPTIGSNVEEIVVKNT
  HFLMWDIGGQESLRSSWNTYYSNTEFIILVVDSIDRERLAITKEELYRMLAHEDLRKAAV
  LIFANKQDMKGCMTAAEISKYLTLSSIKDHPWHIQSCCALTGEGLCQGLEWMTSRIGVR
• Function: Binds and exchanges GTP and GDP.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]
Urolithiasis	DISNFTKT	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Limited	Biomarker	[3]

16 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 ADP-ribosylation factor-like protein 5B (ARL5B).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[13]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[15]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[17]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of ADP-ribosylation factor-like protein 5B (ARL5B).	[18]

References

• [1] GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores.Am J Psychiatry. 2019 Aug 1;176(8):651-660. doi: 10.1176/appi.ajp.2019.18080957. Epub 2019 Jun 5.
• [2] Changing expression profiles of long non-coding RNAs, mRNAs and circular RNAs in ethylene glycol-induced kidney calculi rats.BMC Genomics. 2018 Sep 10;19(1):660. doi: 10.1186/s12864-018-5052-8.
• [3] Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.Oncotarget. 2012 Apr;3(4):399-413. doi: 10.18632/oncotarget.473.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [11] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [17] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [18] 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.