Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZHB2OI)

• DOT Name: Pygopus homolog 2 (PYGO2)
• Gene Name: PYGO2
• Related Disease:
  Glioma
  Ovarian neoplasm
  Adult glioblastoma
  Advanced cancer
  Anaplastic astrocytoma
  Azoospermia
  B-cell neoplasm
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Central nervous system neoplasm
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Inflammatory bowel disease
  Liver cancer
  Male infertility
  Metastatic prostate carcinoma
  Neoplasm
  Obesity
  Oligospermia
  Prostate adenocarcinoma
  Prostate cancer
  Prostate carcinoma
  Type-1/2 diabetes
• UniProt ID: PYGO2_HUMAN
• PDB ID: 2XB1; 4UP0; 4UP5; 8HIB
• Pfam ID: PF00628
• Sequence:
  MAASAPPPPDKLEGGGGPAPPPAPPSTGRKQGKAGLQMKSPEKKRRKSNTQGPAYSHLTE
  FAPPPTPMVDHLVASNPFEDDFGAPKVGVAAPPFLGSPVPFGGFRVQGGMAGQVPPGYST
  GGGGGPQPLRRQPPPFPPNPMGPAFNMPPQGPGYPPPGNMNFPSQPFNQPLGQNFSPPSG
  QMMPGPVGGFGPMISPTMGQPPRAELGPPSLSQRFAQPGAPFGPSPLQRPGQGLPSLPPN
  TSPFPGPDPGFPGPGGEDGGKPLNPPASTAFPQEPHSGSPAAAVNGNQPSFPPNSSGRGG
  GTPDANSLAPPGKAGGGSGPQPPPGLVYPCGACRSEVNDDQDAILCEASCQKWFHRECTG
  MTESAYGLLTTEASAVWACDLCLKTKEIQSVYIREGMGQLVAANDG
• Function: Involved in signal transduction through the Wnt pathway.
• Reactome Pathway:
  Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)
  Formation of the beta-catenin (R-HSA-201722)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioma	DIS5RPEH	Definitive	Altered Expression	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Anaplastic astrocytoma	DISSBE0K	Strong	Biomarker	[4]
Azoospermia	DIS94181	Strong	Genetic Variation	[5]
B-cell neoplasm	DISVY326	Strong	Posttranslational Modification	[6]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[7]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Central nervous system neoplasm	DISFC18W	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[4]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Inflammatory bowel disease	DISGN23E	Strong	Genetic Variation	[11]
Liver cancer	DISDE4BI	Strong	Altered Expression	[10]
Male infertility	DISY3YZZ	Strong	Biomarker	[5]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Obesity	DIS47Y1K	Strong	Biomarker	[13]
Oligospermia	DIS6YJF3	Strong	Biomarker	[5]
Prostate adenocarcinoma	DISBZYU8	Strong	Altered Expression	[14]
Prostate cancer	DISF190Y	Strong	Altered Expression	[14]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[14]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[13]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol increases the phosphorylation of Pygopus homolog 2 (PYGO2).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Pygopus homolog 2 (PYGO2).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Pygopus homolog 2 (PYGO2).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Pygopus homolog 2 (PYGO2).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Pygopus homolog 2 (PYGO2).	[18]

References

• [1] Pygo2 functions as a prognostic factor for glioma due to its up-regulation of H3K4me3 and promotion of MLL1/MLL2 complex recruitment.Sci Rep. 2016 Feb 23;6:22066. doi: 10.1038/srep22066.
• [2] Antisense suppression of pygopus2 results in growth arrest of epithelial ovarian cancer.Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2216-23. doi: 10.1158/1078-0432.CCR-05-2433.
• [3] Decreased pygopus 2 expression suppresses glioblastoma U251 cell growth.J Neurooncol. 2010 Oct;100(1):31-41. doi: 10.1007/s11060-010-0144-6. Epub 2010 Mar 5.
• [4] Immunohistochemistry analysis of Pygo2 expression in central nervous system tumors.J Cell Commun Signal. 2019 Mar;13(1):75-84. doi: 10.1007/s12079-018-0476-0. Epub 2018 Jul 5.
• [5] Associations of single nucleotide polymorphisms in the Pygo2 coding sequence with idiopathic oligospermia and azoospermia.Genet Mol Res. 2015 Aug 7;14(3):9053-61. doi: 10.4238/2015.August.7.14.
• [6] Pygopus2 inhibits the efficacy of paclitaxel-induced apoptosis and induces multidrug resistance in human glioma cells.Oncotarget. 2017 Apr 25;8(17):27915-27928. doi: 10.18632/oncotarget.15843.
• [7] miR-516a-3p inhibits breast cancer cell growth and EMT by blocking the Pygo2/Wnt signalling pathway.J Cell Mol Med. 2019 Sep;23(9):6295-6307. doi: 10.1111/jcmm.14515. Epub 2019 Jul 5.
• [8] Pygo2 activates MDR1 expression and mediates chemoresistance in breast cancer via the Wnt/-catenin pathway.Oncogene. 2016 Sep 8;35(36):4787-97. doi: 10.1038/onc.2016.10. Epub 2016 Feb 15.
• [9] Association of PYGO2 and EGFR in esophageal squamous cell carcinoma.Med Oncol. 2013 Jun;30(2):516. doi: 10.1007/s12032-013-0516-9. Epub 2013 Mar 3.
• [10] Pygopus-2 promotes invasion and metastasis of hepatic carcinoma cell by decreasing E-cadherin expression.Oncotarget. 2015 May 10;6(13):11074-86. doi: 10.18632/oncotarget.3570.
• [11] Identification of Loci at 1q21 and 16q23 That Affect Susceptibility to Inflammatory Bowel Disease in Koreans.Gastroenterology. 2016 Dec;151(6):1096-1099.e4. doi: 10.1053/j.gastro.2016.08.025. Epub 2016 Aug 26.
• [12] An In Vivo Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer.Cancer Res. 2018 Jul 15;78(14):3823-3833. doi: 10.1158/0008-5472.CAN-17-3564. Epub 2018 May 16.
• [13] Pygo2 Regulates Adiposity and Glucose Homeostasis via -Catenin-Axin2-GSK3 Signaling Pathway.Diabetes. 2018 Dec;67(12):2569-2584. doi: 10.2337/db18-0311. Epub 2018 Oct 2.
• [14] PYGOPUS2 expression in prostatic adenocarcinoma is a potential risk stratification marker for PSA progression following radical prostatectomy.J Clin Pathol. 2018 May;71(5):402-411. doi: 10.1136/jclinpath-2017-204718. Epub 2017 Sep 18.
• [15] The G Protein-Coupled Estrogen Receptor Agonist G-1 Inhibits Nuclear Estrogen Receptor Activity and Stimulates Novel Phosphoproteomic Signatures. Toxicol Sci. 2016 Jun;151(2):434-46. doi: 10.1093/toxsci/kfw057. Epub 2016 Mar 29.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Fluorinated N,N-dialkylaminostilbenes for Wnt pathway inhibition and colon cancer repression. J Med Chem. 2011 Mar 10;54(5):1288-97. doi: 10.1021/jm101248v. Epub 2011 Feb 3.
• [18] 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.
• [19] 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.