Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4RWZZD)

• DOT Name: Taste receptor type 2 member 10 (TAS2R10)
• Synonyms: T2R10; Taste receptor family B member 2; TRB2
• Gene Name: TAS2R10
• Related Disease:
  Vascular disease
  Acute myelogenous leukaemia
  Asthma
  Matthew-Wood syndrome
  Neuroblastoma
  Pancreatic cancer
  Pancreatic ductal carcinoma
• UniProt ID: T2R10_HUMAN
• Pfam ID: PF05296
• Sequence:
  MLRVVEGIFIFVVVSESVFGVLGNGFIGLVNCIDCAKNKLSTIGFILTGLAISRIFLIWI
  IITDGFIQIFSPNIYASGNLIEYISYFWVIGNQSSMWFATSLSIFYFLKIANFSNYIFLW
  LKSRTNMVLPFMIVFLLISSLLNFAYIAKILNDYKTKNDTVWDLNMYKSEYFIKQILLNL
  GVIFFFTLSLITCIFLIISLWRHNRQMQSNVTGLRDSNTEAHVKAMKVLISFIILFILYF
  IGMAIEISCFTVRENKLLLMFGMTTTAIYPWGHSFILILGNSKLKQASLRVLQQLKCCEK
  RKNLRVT
• Function: Gustducin-coupled strychnine receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5.
• Tissue Specificity: Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells.
• KEGG Pathway: Taste transduction (hsa04742)
• Reactome Pathway:
  Class C/3 (Metabotropic glutamate/pheromone receptors) (R-HSA-420499)
  Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Vascular disease	DISVS67S	Strong	Altered Expression	[1]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Altered Expression	[2]
Asthma	DISW9QNS	Limited	Genetic Variation	[3]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[4]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[5]
Pancreatic cancer	DISJC981	Limited	Biomarker	[4]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Taste receptor type 2 member 10 (TAS2R10).	[6]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Taste receptor type 2 member 10 (TAS2R10).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Taste receptor type 2 member 10 (TAS2R10).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Taste receptor type 2 member 10 (TAS2R10).	[9]

References

• [1] Tribbles-2 is a novel regulator of inflammatory activation of monocytes.Int Immunol. 2008 Dec;20(12):1543-50. doi: 10.1093/intimm/dxn116. Epub 2008 Oct 24.
• [2] Tribbles-1 and -2 are tumour suppressors, down-regulated in human acute myeloid leukaemia.Immunol Lett. 2010 May 4;130(1-2):115-24. doi: 10.1016/j.imlet.2009.12.007. Epub 2009 Dec 11.
• [3] Association between Polymorphisms in Bitter Taste Receptor Genes and Clinical Features in Korean Asthmatics.Respiration. 2016;91(2):141-50. doi: 10.1159/000443796. Epub 2016 Jan 27.
• [4] Overcoming chemoresistance in pancreatic cancer cells: role of the bitter taste receptor T2R10.J Cancer. 2018 Feb 1;9(4):711-725. doi: 10.7150/jca.21803. eCollection 2018.
• [5] Anti-cancer stemness and anti-invasive activity of bitter taste receptors, TAS2R8 and TAS2R10, in human neuroblastoma cells.PLoS One. 2017 May 3;12(5):e0176851. doi: 10.1371/journal.pone.0176851. eCollection 2017.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [9] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.