Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2BAJHK)

• DOT Name: Dexamethasone-induced Ras-related protein 1 (RASD1)
• Synonyms: Activator of G-protein signaling 1
• Gene Name: RASD1
• Related Disease:
  Advanced cancer
  Aicardi-Goutieres syndrome
  Anaplastic astrocytoma
  Astrocytoma
  Colorectal carcinoma
  Craniosynostosis
  Glioma
  Melanoma
  Metastatic malignant neoplasm
  Multiple sclerosis
  Nervous system inflammation
  Non-small-cell lung cancer
  Optic neuritis
  Plasma cell myeloma
  Prostate cancer
  Prostate neoplasm
  Smith-Magenis syndrome
  Type-1/2 diabetes
  Neoplasm
  Potocki-Lupski syndrome
  Anxiety disorder
  Breast cancer
  Breast carcinoma
  Glioblastoma multiforme
  Non-insulin dependent diabetes
• UniProt ID: RASD1_HUMAN
• Pfam ID: PF00071
• Sequence:
  MKLAAMIKKMCPSDSELSIPAKNCYRMVILGSSKVGKTAIVSRFLTGRFEDAYTPTIEDF
  HRKFYSIRGEVYQLDILDTSGNHPFPAMRRLSILTGDVFILVFSLDNRDSFEEVQRLRQQ
  ILDTKSCLKNKTKENVDVPLVICGNKGDRDFYREVDQREIEQLVGDDPQRCAYFEISAKK
  NSSLDQMFRALFAMAKLPSEMSPDLHRKVSVQYCDVLHKKALRNKKLLRAGSGGGGGDPG
  DAFGIVAPFARRPSVHSDLMYIREKASAGSQAKDKERCVIS
• Function: Small GTPase. Negatively regulates the transcription regulation activity of the APBB1/FE65-APP complex via its interaction with APBB1/FE65.
• Tissue Specificity: Expressed in a variety of tissues including heart, cardiovascular tissues, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, gastrointestinal and reproductive tissues.
• KEGG Pathway:
  Circadian entrainment (hsa04713)
  Cushing syndrome (hsa04934)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Aicardi-Goutieres syndrome	DIS1NH4X	Strong	Genetic Variation	[2]
Anaplastic astrocytoma	DISSBE0K	Strong	Altered Expression	[3]
Astrocytoma	DISL3V18	Strong	Altered Expression	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[4]
Craniosynostosis	DIS6J405	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Melanoma	DIS1RRCY	Strong	Biomarker	[6]
Metastatic malignant neoplasm	DIS86UK6	Strong	Genetic Variation	[7]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[8]
Nervous system inflammation	DISB3X5A	Strong	Genetic Variation	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Optic neuritis	DISDYCHC	Strong	Genetic Variation	[8]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[11]
Smith-Magenis syndrome	DISG4G6X	Strong	Biomarker	[12]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[7]
Neoplasm	DISZKGEW	moderate	Biomarker	[3]
Potocki-Lupski syndrome	DISUOI38	Disputed	Biomarker	[13]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[14]
Breast cancer	DIS7DPX1	Limited	Biomarker	[15]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[16]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[17]

28 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 Dexamethasone-induced Ras-related protein 1 (RASD1).	[18]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[22]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[23]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[24]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[25]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[26]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[26]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[27]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[28]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[25]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[29]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[30]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[31]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[32]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[33]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[34]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[35]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[37]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[40]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[41]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[42]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Dexamethasone-induced Ras-related protein 1 (RASD1).	[43]

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 decreases the methylation of Dexamethasone-induced Ras-related protein 1 (RASD1).	[36]

References

• [1] Vascular Endothelial Growth Factor-A Exerts Diverse Cellular Effects via Small G Proteins, Rho and Rap.Int J Mol Sci. 2018 Apr 16;19(4):1203. doi: 10.3390/ijms19041203.
• [2] Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. Am J Hum Genet. 2007 Apr;80(4):811-5. doi: 10.1086/513443. Epub 2007 Feb 19.
• [3] Overexpression of RASD1 inhibits glioma cell migration/invasion and inactivates the AKT/mTOR signaling pathway.Sci Rep. 2017 Jun 9;7(1):3202. doi: 10.1038/s41598-017-03612-0.
• [4] High expression of Ras-related protein 1A promotes an aggressive phenotype in colorectal cancer via PTEN/FOXO3/CCND1 pathway.J Exp Clin Cancer Res. 2018 Jul 31;37(1):178. doi: 10.1186/s13046-018-0827-y.
• [5] Differentially Regulated Host Proteins Associated with Chronic Rhinosinusitis Are Correlated with the Sinonasal Microbiome.Front Cell Infect Microbiol. 2017 Dec 6;7:504. doi: 10.3389/fcimb.2017.00504. eCollection 2017.
• [6] AT2 Receptor Mediated Activation of the Tyrosine Phosphatase PTP1B Blocks Caveolin-1 Enhanced Migration, Invasion and Metastasis of Cancer Cells.Cancers (Basel). 2019 Sep 3;11(9):1299. doi: 10.3390/cancers11091299.
• [7] Interaction of the Ras-related protein associated with diabetes rad and the putative tumor metastasis suppressor NM23 provides a novel mechanism of GTPase regulation.Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14911-8. doi: 10.1073/pnas.96.26.14911.
• [8] Dexras1 Deletion and Iron Chelation Promote Neuroprotection in Experimental Optic Neuritis.Sci Rep. 2019 Aug 12;9(1):11664. doi: 10.1038/s41598-019-48087-3.
• [9] microRNA-338-3p functions as a tumor suppressor in human nonsmallcell lung carcinoma and targets Ras-related protein 14.Mol Med Rep. 2015 Feb;11(2):1400-6. doi: 10.3892/mmr.2014.2880. Epub 2014 Nov 6.
• [10] Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma.Clin Cancer Res. 2009 Jul 1;15(13):4356-64. doi: 10.1158/1078-0432.CCR-08-3336. Epub 2009 Jun 23.
• [11] Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.Prostate. 2007 Jan 1;67(1):83-106. doi: 10.1002/pros.20505.
• [12] Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.Am J Respir Cell Mol Biol. 2018 Mar;58(3):391-401. doi: 10.1165/rcmb.2017-0237OC.
• [13] Circadian abnormalities in mouse models of Smith-Magenis syndrome: evidence for involvement of RAI1.Am J Med Genet A. 2013 Jul;161A(7):1561-8. doi: 10.1002/ajmg.a.35941. Epub 2013 May 23.
• [14] Hippocampal nuclear factor kappa B accounts for stress-induced anxiety behaviors via enhancing neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS-Dexras1 coupling.J Neurochem. 2018 Sep;146(5):598-612. doi: 10.1111/jnc.14478. Epub 2018 Aug 2.
• [15] Increased expression of Rab25 in breast cancer correlates with lymphatic metastasis.Tumour Biol. 2012 Oct;33(5):1581-7. doi: 10.1007/s13277-012-0412-5. Epub 2012 May 30.
• [16] Knockdown of Ras-Related Protein 25 (Rab25) Inhibits the In Vitro Cytotoxicity and In Vivo Antitumor Activity of Human Glioblastoma Multiforme Cells.Oncol Res. 2017 Mar 13;25(3):331-340. doi: 10.3727/096504016X14736286083065.
• [17] Genetics of non-insulin-dependent (type-II) diabetes mellitus.Annu Rev Med. 1996;47:509-31. doi: 10.1146/annurev.med.47.1.509.
• [18] 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.
• [19] 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.
• [20] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [21] 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.
• [22] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [23] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [24] 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.
• [25] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [26] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [27] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [28] 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.
• [29] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [30] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [31] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [32] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [33] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [34] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [35] Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J. 2009 Mar 4;28(5):523-32.
• [36] 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.
• [37] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [38] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [39] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [40] Identification of gene markers for formaldehyde exposure in humans. Environ Health Perspect. 2007 Oct;115(10):1460-6. doi: 10.1289/ehp.10180.
• [41] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [42] 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.
• [43] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.