Details of Drug Off-Target (DOT)

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

• DOT Name: Protein phosphatase inhibitor 2 (PPP1R2)
• Synonyms: IPP-2
• Gene Name: PPP1R2
• Related Disease:
  Breast cancer
  Breast carcinoma
  Advanced cancer
  Non-insulin dependent diabetes
  Prostate cancer
  Prostate carcinoma
• UniProt ID: IPP2_HUMAN
• Pfam ID: PF04979
• Sequence:
  MAASTASHRPIKGILKNKTSTTSSMVASAEQPRGNVDEELSKKSQKWDEMNILATYHPAD
  KDYGLMKIDEPSTPYHSMMGDDEDACSDTEATEAMAPDILARKLAAAEGLEPKYRIQEQE
  SSGEEDSDLSPEEREKKRQFEMKRKLHYNEGLNIKLARQLISKDLHDDDEDEEMLETADG
  ESMNTEESNQGSTPSDQQQNKLRSS
• Function: Inhibitor of protein-phosphatase 1.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[3]
Prostate cancer	DISF190Y	Limited	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitoxantrone	DMM39BF	Approved	Protein phosphatase inhibitor 2 (PPP1R2) affects the response to substance of Mitoxantrone.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Protein phosphatase inhibitor 2 (PPP1R2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein phosphatase inhibitor 2 (PPP1R2).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein phosphatase inhibitor 2 (PPP1R2).	[16]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Protein phosphatase inhibitor 2 (PPP1R2).	[16]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Protein phosphatase inhibitor 2 (PPP1R2).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[8]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[10]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[11]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[12]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[14]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein phosphatase inhibitor 2 (PPP1R2).	[17]

References

• [1] Dopamine and cAMP-regulated phosphoprotein 32kDa (DARPP-32) and survival in breast cancer: a retrospective analysis of protein and mRNA expression.Sci Rep. 2019 Nov 18;9(1):16987. doi: 10.1038/s41598-019-53529-z.
• [2] Protein phosphatase 1 and its complexes in carcinogenesis.Curr Cancer Drug Targets. 2014;14(1):2-29. doi: 10.2174/15680096113136660106.
• [3] Genetic analysis of human type 1 protein phosphatase inhibitor 2 in insulin-resistant Pima Indians.Genomics. 1997 Apr 1;41(1):110-4. doi: 10.1006/geno.1997.4649.
• [4] TGF- cascade regulation by PPP1 and its interactors -impact on prostate cancer development and therapy.J Cell Mol Med. 2014 Apr;18(4):555-67. doi: 10.1111/jcmm.12266. Epub 2014 Mar 15.
• [5] 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.
• [6] 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.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [10] 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.
• [11] Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
• [12] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [13] Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
• [14] Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17. doi: 10.1158/0008-5472.CAN-07-2464.
• [15] 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.
• [16] 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.
• [17] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [18] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [19] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.