Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8L4L2R)

• DOT Name: Pygopus homolog 1 (PYGO1)
• Gene Name: PYGO1
• UniProt ID: PYGO1_HUMAN
• PDB ID: 2VP7; 2VPB; 2VPD; 2VPE; 2VPG
• Pfam ID: PF00628
• Sequence:
  MPAENSPAPAYKVSSHGGDSGLDGLGGPGVQLGSPDKKKRKANTQGPSFPPLSEYAPPPN
  PNSDHLVAANPFDDNYNTISYKPLPSSNPYLGPGYPGFGGYSTFRMPPHVPPRMSSPYCG
  PYSLRNQPHPFPQNPLGMGFNRPHAFNFGPHDNSSFGNPSYNNALSQNVNMPNQHFRQNP
  AENFSQIPPQNASQVSNPDLASNFVPGNNSNFTSPLESNHSFIPPPNTFGQAKAPPPKQD
  FTQGATKNTNQNSSAHPPHLNMDDTVNQSNIELKNVNRNNAVNQENSRSSSTEATNNNPA
  NGTQNKPRQPRGAADACTTEKSNKSSLHPNRHGHSSSDPVYPCGICTNEVNDDQDAILCE
  ASCQKWFHRICTGMTETAYGLLTAEASAVWGCDTCMADKDVQLMRTRETFGPSAVGSDA
• 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

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Pygopus homolog 1 (PYGO1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pygopus homolog 1 (PYGO1).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Pygopus homolog 1 (PYGO1).	[3]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Pygopus homolog 1 (PYGO1).	[4]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Pygopus homolog 1 (PYGO1).	[5]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Pygopus homolog 1 (PYGO1).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Pygopus homolog 1 (PYGO1).	[8]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Pygopus homolog 1 (PYGO1).	[9]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Pygopus homolog 1 (PYGO1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Pygopus homolog 1 (PYGO1).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] 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.
• [5] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [10] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.