Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIAZ36F)

• DOT Name: Regulator of G-protein signaling 11 (RGS11)
• Synonyms: RGS11
• Gene Name: RGS11
• Related Disease:
  Lung cancer
  Lung carcinoma
  Neoplasm
  Ankylosing spondylitis
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Lung adenocarcinoma
• UniProt ID: RGS11_HUMAN
• Pfam ID: PF00610 ; PF00631 ; PF00615 ; PF18148
• Sequence:
  MAAGPAPPPGRPRAQMPHLRKMERVVVSMQDPDQGVKMRSQRLLVTVIPHAVTGSDVVQW
  LAQKFCVSEEEALHLGAVLVQHGYIYPLRDPRSLMLRPDETPYRFQTPYFWTSTLRPAAE
  LDYAIYLAKKNIRKRGTLVDYEKDCYDRLHKKINHAWDLVLMQAREQLRAAKQRSKGDRL
  VIACQEQTYWLVNRPPPGAPDVLEQGPGRGSCAASRVLMTKSADFHKREIEYFRKALGRT
  RVKSSVCLEAYLSFCGQRGPHDPLVSGCLPSNPWISDNDAYWVMNAPTVAAPTKLRVERW
  GFSFRELLEDPVGRAHFMDFLGKEFSGENLSFWEACEELRYGAQAQVPTLVDAVYEQFLA
  PGAAHWVNIDSRTMEQTLEGLRQPHRYVLDDAQLHIYMLMKKDSYPRFLKSDMYKALLAE
  AGIPLEMKRRVFPFTWRPRHSSPSPALLPTPVEPTAACGPGGGDGVA
• Function: Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.
• Reactome Pathway:
  Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding (R-HSA-6814122)
  G alpha (i) signalling events (R-HSA-418594)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung cancer	DISCM4YA	Strong	Altered Expression	[1]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]
Ankylosing spondylitis	DISRC6IR	moderate	Biomarker	[3]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]
Breast cancer	DIS7DPX1	Limited	Biomarker	[5]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[5]
Lung adenocarcinoma	DISD51WR	Limited	Altered Expression	[4]

2 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 11 (RGS11).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Regulator of G-protein signaling 11 (RGS11).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Regulator of G-protein signaling 11 (RGS11).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Regulator of G-protein signaling 11 (RGS11).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Regulator of G-protein signaling 11 (RGS11).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Regulator of G-protein signaling 11 (RGS11).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Regulator of G-protein signaling 11 (RGS11).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Regulator of G-protein signaling 11 (RGS11).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Regulator of G-protein signaling 11 (RGS11).	[12]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Regulator of G-protein signaling 11 (RGS11).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Regulator of G-protein signaling 11 (RGS11).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Regulator of G-protein signaling 11 (RGS11).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Regulator of G-protein signaling 11 (RGS11).	[17]

References

• [1] Diagnosing the RGS11 Lung Cancer Biomarker: The Integration of Competitive Immunoassay and Isothermal Nucleic Acid Exponential Amplification Reaction.Anal Chem. 2019 Mar 5;91(5):3327-3335. doi: 10.1021/acs.analchem.8b04374. Epub 2019 Feb 15.
• [2] Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multicenter trial.J Surg Oncol. 2017 Jun;115(8):917-923. doi: 10.1002/jso.24610. Epub 2017 Apr 13.
• [3] Familial aggregation of Reiter's syndrome and ankylosing spondylitis: a comparative study.J Rheumatol. 1984 Oct;11(5):672-7.
• [4] Overexpression of regulator of G protein signaling 11 promotes cell migration and associates with advanced stages and aggressiveness of lung adenocarcinoma.Oncotarget. 2016 May 24;7(21):31122-36. doi: 10.18632/oncotarget.8860.
• [5] Evaluation of the Incorporation of Recurrence Score into the American Joint Committee on Cancer Eighth Edition Staging System in Patients with T1-2N0M0, Estrogen Receptor-Positive, Human Epidermal Growth Receptor 2-Negative Invasive Breast Cancer: A Population-Based Analysis.Oncologist. 2019 Nov;24(11):e1014-e1023. doi: 10.1634/theoncologist.2018-0727. Epub 2019 Apr 24.
• [6] 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.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] 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.
• [14] 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.
• [15] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.