Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRL8IUO)

• DOT Name: Ras-related protein Rab-37 (RAB37)
• Gene Name: RAB37
• Related Disease:
  Non-small-cell lung cancer
  Advanced cancer
  Clear cell renal carcinoma
  Esophageal squamous cell carcinoma
  Lung neoplasm
  Neoplasm
  Papillary renal cell carcinoma
  Renal cell carcinoma
  Coronary heart disease
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
• UniProt ID: RAB37_HUMAN
• Pfam ID: PF00071
• Sequence:
  MTGTPGAVATRDGEAPERSPPCSPSYDLTGKVMLLGDTGVGKTCFLIQFKDGAFLSGTFI
  ATVGIDFRNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLYDITNKSSFDN
  IRAWLTEIHEYAQRDVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNV
  ELAFLAIAKELKYRAGHQADEPSFQIRDYVESQKKRSSCCSFM
• Reactome Pathway:
  RAB geranylgeranylation (R-HSA-8873719)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Posttranslational Modification	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[3]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[4]
Lung neoplasm	DISVARNB	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Papillary renal cell carcinoma	DIS25HBV	Strong	Genetic Variation	[7]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[3]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[8]
Lung cancer	DISCM4YA	moderate	Biomarker	[5]
Lung carcinoma	DISTR26C	moderate	Biomarker	[5]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ras-related protein Rab-37 (RAB37).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Ras-related protein Rab-37 (RAB37).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ras-related protein Rab-37 (RAB37).	[20]

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ras-related protein Rab-37 (RAB37).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ras-related protein Rab-37 (RAB37).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ras-related protein Rab-37 (RAB37).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras-related protein Rab-37 (RAB37).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ras-related protein Rab-37 (RAB37).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ras-related protein Rab-37 (RAB37).	[16]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Ras-related protein Rab-37 (RAB37).	[17]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Ras-related protein Rab-37 (RAB37).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Ras-related protein Rab-37 (RAB37).	[19]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Ras-related protein Rab-37 (RAB37).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Ras-related protein Rab-37 (RAB37).	[22]

References

• [1] Frequent down-regulation of hRAB37 in metastatic tumor by genetic and epigenetic mechanisms in lung cancer.Lung Cancer. 2009 Mar;63(3):360-7. doi: 10.1016/j.lungcan.2008.06.014. Epub 2008 Aug 8.
• [2] VAMP8, a vesicle-SNARE required for RAB37-mediated exocytosis, possesses a tumor metastasis suppressor function.Cancer Lett. 2018 Nov 28;437:79-88. doi: 10.1016/j.canlet.2018.08.023. Epub 2018 Aug 27.
• [3] Involvement of TMEM22 overexpression in the growth of renal cell carcinoma cells.Oncol Rep. 2009 Feb;21(2):305-12.
• [4] Dysregulation of Rab37-Mediated Cross-talk between Cancer Cells and Endothelial Cells via Thrombospondin-1 Promotes Tumor Neovasculature and Metastasis.Clin Cancer Res. 2017 May 1;23(9):2335-2345. doi: 10.1158/1078-0432.CCR-16-1520. Epub 2016 Nov 15.
• [5] Rab37 in lung cancer mediates exocytosis of soluble ST2 and thus skews macrophages toward tumor-suppressing phenotype.Int J Cancer. 2018 Oct 1;143(7):1753-1763. doi: 10.1002/ijc.31569. Epub 2018 Jul 3.
• [6] Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness.Cell Death Dis. 2018 Aug 29;9(9):868. doi: 10.1038/s41419-018-0915-0.
• [7] Papillary renal cell carcinoma: a clinicopathological and whole-genome exon sequencing study.Int J Clin Exp Pathol. 2015 Jul 1;8(7):8311-35. eCollection 2015.
• [8] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [9] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [10] 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.
• [11] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [12] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] 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.
• [15] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [16] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [17] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [18] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [19] 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.
• [20] 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.
• [21] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [22] 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.