Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ8N1QH)

• DOT Name: Regulator of G-protein signaling 10 (RGS10)
• Synonyms: RGS10
• Gene Name: RGS10
• Related Disease:
  Age-related macular degeneration
  Bone disease
  Depression
  Epithelial ovarian cancer
  Neuralgia
  Ovarian cancer
  Ovarian neoplasm
  Neoplasm
  Parkinson disease
• UniProt ID: RGS10_HUMAN
• PDB ID: 2DLR; 2I59; 2IHB
• Pfam ID: PF00615
• Sequence:
  MFNRAVSRLSRKRPPSDIHDSDGSSSSSHQSLKSTAKWAASLENLLEDPEGVKRFREFLK
  KEFSEENVLFWLACEDFKKMQDKTQMQEKAKEIYMTFLSSKASSQVNVEGQSRLNEKILE
  EPHPLMFQKLQDQIFNLMKYDSYSRFLKSDLFLKHKRTEEEEEDLPDAQTAAKRASRIYN
  T
• Function: Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the muscarinic acetylcholine receptor CHRM2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Modulates the activity of potassium channels that are activated in response to CHRM2 signaling. Activity on GNAZ is inhibited by palmitoylation of the G-protein.
• Reactome Pathway: G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Genetic Variation	[1]
Bone disease	DISE1F82	Strong	Biomarker	[2]
Depression	DIS3XJ69	Strong	Biomarker	[3]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[4]
Neuralgia	DISWO58J	Strong	Altered Expression	[5]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[4]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Limited	Posttranslational Modification	[4]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Docetaxel	DMDI269	Approved	Regulator of G-protein signaling 10 (RGS10) increases the response to substance of Docetaxel.	[11]

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 Regulator of G-protein signaling 10 (RGS10).	[7]

17 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 Regulator of G-protein signaling 10 (RGS10).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Regulator of G-protein signaling 10 (RGS10).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Regulator of G-protein signaling 10 (RGS10).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Regulator of G-protein signaling 10 (RGS10).	[11]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Regulator of G-protein signaling 10 (RGS10).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Regulator of G-protein signaling 10 (RGS10).	[13]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Regulator of G-protein signaling 10 (RGS10).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Regulator of G-protein signaling 10 (RGS10).	[15]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Regulator of G-protein signaling 10 (RGS10).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Regulator of G-protein signaling 10 (RGS10).	[17]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Regulator of G-protein signaling 10 (RGS10).	[18]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Regulator of G-protein signaling 10 (RGS10).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Regulator of G-protein signaling 10 (RGS10).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Regulator of G-protein signaling 10 (RGS10).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Regulator of G-protein signaling 10 (RGS10).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Regulator of G-protein signaling 10 (RGS10).	[21]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Regulator of G-protein signaling 10 (RGS10).	[22]

References

• [1] Age-related changes in regulator of G-protein signaling (RGS)-10 expression in peripheral and central immune cells may influence the risk for age-related degeneration.Neurobiol Aging. 2015 May;36(5):1982-93. doi: 10.1016/j.neurobiolaging.2015.02.006. Epub 2015 Feb 13.
• [2] RGS10-null mutation impairs osteoclast differentiation resulting from the loss of [Ca2+]i oscillation regulation.Genes Dev. 2007 Jul 15;21(14):1803-16. doi: 10.1101/gad.1544107. Epub 2007 Jul 12.
• [3] Gene-level genome-wide association analysis of suicide attempt, a preliminary study in a psychiatric Mexican population.Mol Genet Genomic Med. 2019 Dec;7(12):e983. doi: 10.1002/mgg3.983. Epub 2019 Oct 2.
• [4] Inhibition of HDAC1 and DNMT1 modulate RGS10 expression and decrease ovarian cancer chemoresistance.PLoS One. 2014 Jan 27;9(1):e87455. doi: 10.1371/journal.pone.0087455. eCollection 2014.
• [5] Regulator of G Protein Signaling 10 (Rgs10) Expression Is Transcriptionally Silenced in Activated Microglia by Histone Deacetylase Activity.Mol Pharmacol. 2017 Mar;91(3):197-207. doi: 10.1124/mol.116.106963. Epub 2016 Dec 28.
• [6] Regulator of G-protein signaling-10 negatively regulates NF-B in microglia and neuroprotects dopaminergic neurons in hemiparkinsonian rats.J Neurosci. 2011 Aug 17;31(33):11879-88. doi: 10.1523/JNEUROSCI.1002-11.2011.
• [7] 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.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells. Mol Cancer. 2010 Nov 2;9:289. doi: 10.1186/1476-4598-9-289.
• [12] 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.
• [13] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [14] 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.
• [15] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [20] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [21] 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.
• [22] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [23] Regulators of G-Protein signaling RGS10 and RGS17 regulate chemoresistance in ovarian cancer cells. Mol Cancer. 2010 Nov 2;9:289. doi: 10.1186/1476-4598-9-289.