Details of Drug Off-Target (DOT)

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

• DOT Name: Ras-related protein Rab-26 (RAB26)
• Gene Name: RAB26
• Related Disease:
  Lung cancer
  Lung carcinoma
  Non-small-cell lung cancer
  Vascular disease
• UniProt ID: RAB26_HUMAN
• PDB ID: 2G6B
• Pfam ID: PF00071
• Sequence:
  MSRKKTPKSKGASTPAASTLPTANGARPARSGTALSGPDAPPNGPLQPGRPSLGGGVDFY
  DVAFKVMLVGDSGVGKTCLLVRFKDGAFLAGTFISTVGIDFRNKVLDVDGVKVKLQMWDT
  AGQERFRSVTHAYYRDAHALLLLYDVTNKASFDNIQAWLTEIHEYAQHDVALMLLGNKVD
  SAHERVVKREDGEKLAKEYGLPFMETSAKTGLNVDLAFTAIAKELKQRSMKAPSEPRFRL
  HDYVKREGRGASCCRP
• Function: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. Mediates transport of ADRA2A and ADRA2B from the Golgi to the cell membrane. Plays a role in the maturation of zymogenic granules and in pepsinogen secretion in the stomach. Plays a role in the secretion of amylase from acinar granules in the parotid gland.
• Tissue Specificity: Predominantly expressed in brain.
• 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
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Vascular disease	DISVS67S	Strong	Biomarker	[2]

1 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-26 (RAB26).	[3]

19 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-26 (RAB26).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ras-related protein Rab-26 (RAB26).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ras-related protein Rab-26 (RAB26).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ras-related protein Rab-26 (RAB26).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Ras-related protein Rab-26 (RAB26).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ras-related protein Rab-26 (RAB26).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Ras-related protein Rab-26 (RAB26).	[10]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Ras-related protein Rab-26 (RAB26).	[11]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Ras-related protein Rab-26 (RAB26).	[12]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Ras-related protein Rab-26 (RAB26).	[13]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Ras-related protein Rab-26 (RAB26).	[10]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Ras-related protein Rab-26 (RAB26).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ras-related protein Rab-26 (RAB26).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ras-related protein Rab-26 (RAB26).	[15]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Ras-related protein Rab-26 (RAB26).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ras-related protein Rab-26 (RAB26).	[17]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ras-related protein Rab-26 (RAB26).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ras-related protein Rab-26 (RAB26).	[19]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Ras-related protein Rab-26 (RAB26).	[20]

References

• [1] Targeted Delivery of Rab26 siRNA with Precisely Tailored DNA Prism for Lung Cancer Therapy.Chembiochem. 2019 May 2;20(9):1139-1144. doi: 10.1002/cbic.201800761. Epub 2019 Feb 27.
• [2] Regulation on Toll-like Receptor 4 and Cell Barrier Function by Rab26 siRNA-loaded DNA Nanovector in Pulmonary Microvascular Endothelial Cells.Theranostics. 2017 Jun 25;7(9):2537-2554. doi: 10.7150/thno.17584. eCollection 2017.
• [3] 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.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [11] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [12] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [13] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [17] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [18] 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.
• [19] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [20] Vesicle transport related protein Synaptotagmin-1 mediates paraquat transport to antagonize paraquat toxicity. Toxicology. 2022 Apr 30;472:153180. doi: 10.1016/j.tox.2022.153180. Epub 2022 Apr 18.