Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT98M6UI)

• DOT Name: Rho-related GTP-binding protein RhoN (RND2)
• Synonyms: Rho family GTPase 2; Rho-related GTP-binding protein Rho7; Rnd2
• Gene Name: RND2
• UniProt ID: RND2_HUMAN
• Pfam ID: PF00071
• Sequence:
  MEGQSGRCKIVVVGDAECGKTALLQVFAKDAYPGSYVPTVFENYTASFEIDKRRIELNMW
  DTSGSSYYDNVRPLAYPDSDAVLICFDISRPETLDSVLKKWQGETQEFCPNAKVVLVGCK
  LDMRTDLATLRELSKQRLIPVTHEQGTVLAKQVGAVSYVECSSRSSERSVRDVFHVATVA
  SLGRGHRQLRRTDSRRGMQRSAQLSGRPDRGNEGEIHKDRAKSCNLM
• Function: May be specifically involved in neuronal and hepatic functions. Is a C3 toxin-insensitive member of the Rho subfamily.
• Tissue Specificity: Highly expressed in testis.
• Reactome Pathway: RND2 GTPase cycle (R-HSA-9696270)

Molecular Interaction Atlas (MIA) of This DOT

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 Rho-related GTP-binding protein RhoN (RND2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Rho-related GTP-binding protein RhoN (RND2).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Rho-related GTP-binding protein RhoN (RND2).	[6]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Rho-related GTP-binding protein RhoN (RND2).	[4]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Rho-related GTP-binding protein RhoN (RND2).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[8]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Rho-related GTP-binding protein RhoN (RND2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Rho-related GTP-binding protein RhoN (RND2).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Rho-related GTP-binding protein RhoN (RND2).	[16]

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 Rho-related GTP-binding protein RhoN (RND2).	[11]

References

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• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] 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.
• [4] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] 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.
• [7] 5-Fluorouracil up-regulates interferon pathway gene expression in esophageal cancer cells. Anticancer Res. 2005 Sep-Oct;25(5):3271-8.
• [8] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [9] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] 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.
• [14] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [15] 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.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.