Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0A9AVD)

• DOT Name: Transient receptor potential cation channel subfamily V member 2 (TRPV2)
• Synonyms: TrpV2; Osm-9-like TRP channel 2; OTRPC2; Vanilloid receptor-like protein 1; VRL-1
• Gene Name: TRPV2
• UniProt ID: TRPV2_HUMAN
• PDB ID: 2F37
• Pfam ID: PF12796 ; PF00520
• Sequence:
  MTSPSSSPVFRLETLDGGQEDGSEADRGKLDFGSGLPPMESQFQGEDRKFAPQIRVNLNY
  RKGTGASQPDPNRFDRDRLFNAVSRGVPEDLAGLPEYLSKTSKYLTDSEYTEGSTGKTCL
  MKAVLNLKDGVNACILPLLQIDRDSGNPQPLVNAQCTDDYYRGHSALHIAIEKRSLQCVK
  LLVENGANVHARACGRFFQKGQGTCFYFGELPLSLAACTKQWDVVSYLLENPHQPASLQA
  TDSQGNTVLHALVMISDNSAENIALVTSMYDGLLQAGARLCPTVQLEDIRNLQDLTPLKL
  AAKEGKIEIFRHILQREFSGLSHLSRKFTEWCYGPVRVSLYDLASVDSCEENSVLEIIAF
  HCKSPHRHRMVVLEPLNKLLQAKWDLLIPKFFLNFLCNLIYMFIFTAVAYHQPTLKKQAA
  PHLKAEVGNSMLLTGHILILLGGIYLLVGQLWYFWRRHVFIWISFIDSYFEILFLFQALL
  TVVSQVLCFLAIEWYLPLLVSALVLGWLNLLYYTRGFQHTGIYSVMIQKVILRDLLRFLL
  IYLVFLFGFAVALVSLSQEAWRPEAPTGPNATESVQPMEGQEDEGNGAQYRGILEASLEL
  FKFTIGMGELAFQEQLHFRGMVLLLLLAYVLLTYILLLNMLIALMSETVNSVATDSWSIW
  KLQKAISVLEMENGYWWCRKKQRAGVMLTVGTKPDGSPDERWCFRVEEVNWASWEQTLPT
  LCEDPSGAGVPRTLENPVLASPPKEDEDGASEENYVPVQLLQSN
• Function: Calcium-permeable, non-selective cation channel with an outward rectification. Seems to be regulated, at least in part, by IGF-I, PDGF and neuropeptide head activator. May transduce physical stimuli in mast cells. Activated by temperatures higher than 52 degrees Celsius; is not activated by vanilloids and acidic pH.
• KEGG Pathway:
  NOD-like receptor sig.ling pathway (hsa04621)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway: TRP channels (R-HSA-3295583)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Transient receptor potential cation channel subfamily V member 2 (TRPV2) increases the response to substance of Cisplatin.	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[5]
Marinol	DM70IK5	Approved	Marinol increases the activity of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[7]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the activity of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[8]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[9]
Tranilast	DME5Y64	Approved	Tranilast decreases the activity of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[10]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[15]

2 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 Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Transient receptor potential cation channel subfamily V member 2 (TRPV2).	[14]

References

• [1] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [5] 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.
• [6] Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity. Chem Res Toxicol. 2018 May 21;31(5):291-301. doi: 10.1021/acs.chemrestox.7b00336. Epub 2018 Apr 30.
• [7] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [8] TRPV2 is activated by cannabidiol and mediates CGRP release in cultured rat dorsal root ganglion neurons. J Neurosci. 2008 Jun 11;28(24):6231-8.
• [9] 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.
• [10] Ca(2+) Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2. Int J Mol Sci. 2018 Sep 19;19(9):2829. doi: 10.3390/ijms19092829.
• [11] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [12] 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.
• [13] 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.
• [14] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [15] 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.
• [16] The Effects of Cannabidiol and Prognostic Role of TRPV2 in Human Endometrial Cancer. Int J Mol Sci. 2020 Jul 29;21(15):5409. doi: 10.3390/ijms21155409.