Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGY8ESX)

• DOT Name: Protein canopy homolog 2 (CNPY2)
• Synonyms: MIR-interacting saposin-like protein; Putative secreted protein Zsig9; Transmembrane protein 4
• Gene Name: CNPY2
• Related Disease:
  Adenocarcinoma
  Cardiac failure
  Colorectal carcinoma
  Congestive heart failure
  Esophageal squamous cell carcinoma
  Familial adenomatous polyposis 2
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Myocardial infarction
  Neoplasm
  Non-small-cell lung cancer
  Pancreatitis
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Clear cell renal carcinoma
  Renal cell carcinoma
  Colorectal neoplasm
  Hepatocellular carcinoma
• UniProt ID: CNPY2_HUMAN
• Pfam ID: PF11938
• Sequence:
  MKGWGWLALLLGALLGTAWARRSQDLHCGACRALVDELEWEIAQVDPKKTIQMGSFRINP
  DGSQSVVEVPYARSEAHLTELLEEICDRMKEYGEQIDPSTHRKNYVRVVGRNGESSELDL
  QGIRIDSDISGTLKFACESIVEEYEDELIEFFSREADNVKDKLCSKRTDLCDHALHISHD
  EL
• Function: Positive regulator of neurite outgrowth by stabilizing myosin regulatory light chain (MRLC). It prevents MIR-mediated MRLC ubiquitination and its subsequent proteasomal degradation.
• Tissue Specificity: Expressed in different tissues. Highest levels are detected in adult placenta, liver and pancreas.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Cardiac failure	DISDC067	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Genetic Variation	[4]
Familial adenomatous polyposis 2	DIS62W3Y	Strong	Genetic Variation	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[6]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[6]
Myocardial infarction	DIS655KI	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[1]
Pancreatitis	DIS0IJEF	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[9]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	moderate	Altered Expression	[10]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[10]
Colorectal neoplasm	DISR1UCN	Limited	Altered Expression	[11]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein canopy homolog 2 (CNPY2).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein canopy homolog 2 (CNPY2).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein canopy homolog 2 (CNPY2).	[14]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein canopy homolog 2 (CNPY2).	[15]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein canopy homolog 2 (CNPY2).	[16]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein canopy homolog 2 (CNPY2).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein canopy homolog 2 (CNPY2).	[18]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein canopy homolog 2 (CNPY2).	[19]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Protein canopy homolog 2 (CNPY2).	[20]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Protein canopy homolog 2 (CNPY2).	[21]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Protein canopy homolog 2 (CNPY2).	[22]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein canopy homolog 2 (CNPY2).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein canopy homolog 2 (CNPY2).	[24]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein canopy homolog 2 (CNPY2).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein canopy homolog 2 (CNPY2).	[25]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein canopy homolog 2 (CNPY2).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein canopy homolog 2 (CNPY2).	[27]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Protein canopy homolog 2 (CNPY2).	[28]

References

• [1] The CNPY2 enhances epithelial-mesenchymal transition via activating the AKT/GSK3 pathway in non-small cell lung cancer.Cell Biol Int. 2018 Aug;42(8):959-964. doi: 10.1002/cbin.10961. Epub 2018 Apr 17.
• [2] Knockout of Canopy 2 activates p16(INK4a) pathway to impair cardiac repair.J Mol Cell Cardiol. 2019 Jul;132:36-48. doi: 10.1016/j.yjmcc.2019.04.018. Epub 2019 Apr 29.
• [3] Serum CNPY2 isoform 2 represents a novel biomarker for early detection of colorectal cancer.Aging (Albany NY). 2018 Aug 2;10(8):1921-1931. doi: 10.18632/aging.101512.
• [4] A decision tree-based combination of ezrin-interacting proteins to estimate the prognostic risk of patients with esophageal squamous cell carcinoma.Hum Pathol. 2017 Aug;66:115-125. doi: 10.1016/j.humpath.2017.06.003. Epub 2017 Jun 9.
• [5] Soluble urokinase plasminogen activator receptor associates with higher risk, advanced disease severity as well as inflammation, and might serve as a prognostic biomarker of severe acute pancreatitis.J Clin Lab Anal. 2020 Mar;34(3):e23097. doi: 10.1002/jcla.23097. Epub 2019 Nov 27.
• [6] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [7] Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage.Cell Physiol Biochem. 2018;50(6):2017-2028. doi: 10.1159/000495048. Epub 2018 Nov 9.
• [8] From moderately severe to severe hypertriglyceridemia induced acute pancreatitis: circulating miRNAs play role as potential biomarkers.PLoS One. 2014 Nov 3;9(11):e111058. doi: 10.1371/journal.pone.0111058. eCollection 2014.
• [9] CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells.Oncotarget. 2018 Apr 3;9(25):17645-17655. doi: 10.18632/oncotarget.24824. eCollection 2018 Apr 3.
• [10] CNPY2 promoted the proliferation of renal cell carcinoma cells and increased the expression of TP53.Biochem Biophys Res Commun. 2017 Apr 1;485(2):267-271. doi: 10.1016/j.bbrc.2017.02.095. Epub 2017 Feb 21.
• [11] Decreasing CNPY2 Expression Diminishes Colorectal Tumor Growth and Development through Activation of p53 Pathway.Am J Pathol. 2016 Apr;186(4):1015-24. doi: 10.1016/j.ajpath.2015.11.012. Epub 2016 Feb 3.
• [12] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [15] 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.
• [16] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [17] 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.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] 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.
• [20] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [21] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [22] Proteomics analysis of the proliferative effect of low-dose ouabain on human endothelial cells. Biol Pharm Bull. 2007 Feb;30(2):247-53. doi: 10.1248/bpb.30.247.
• [23] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [24] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [25] Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib. Blood. 2015 Sep 24;126(13):1565-74.
• [26] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [27] 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.
• [28] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.