Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY5IE69)

• DOT Name: Protein phosphatase 1 regulatory subunit 7 (PPP1R7)
• Synonyms: Protein phosphatase 1 regulatory subunit 22
• Gene Name: PPP1R7
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Neoplasm
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Cervical carcinoma
• UniProt ID: PP1R7_HUMAN
• PDB ID: 6HKW; 6MKY; 6OBN; 6OBP; 8B5R; 8U5G
• Pfam ID: PF12799 ; PF14580
• Sequence:
  MAAERGAGQQQSQEMMEVDRRVESEESGDEEGKKHSSGIVADLSEQSLKDGEERGEEDPE
  EEHELPVDMETINLDRDAEDVDLNHYRIGKIEGFEVLKKVKTLCLRQNLIKCIENLEELQ
  SLRELDLYDNQIKKIENLEALTELEILDISFNLLRNIEGVDKLTRLKKLFLVNNKISKIE
  NLSNLHQLQMLELGSNRIRAIENIDTLTNLESLFLGKNKITKLQNLDALTNLTVLSMQSN
  RLTKIEGLQNLVNLRELYLSHNGIEVIEGLENNNKLTMLDIASNRIKKIENISHLTELQE
  FWMNDNLLESWSDLDELKGARSLETVYLERNPLQKDPQYRRKVMLALPSVRQIDATFVRF
• Function: Regulatory subunit of protein phosphatase 1.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[2]
Breast cancer	DIS7DPX1	moderate	Biomarker	[2]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[2]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[3]

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 Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[11]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[12]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein phosphatase 1 regulatory subunit 7 (PPP1R7).	[17]

References

• [1] Rearrangement of the Protein Phosphatase 1 Interactome During Heart Failure Progression.Circulation. 2018 Oct 9;138(15):1569-1581. doi: 10.1161/CIRCULATIONAHA.118.034361.
• [2] Protein Phosphatase 1 Regulatory Subunit SDS22 Inhibits Breast Cancer Cell Tumorigenesis by Functioning as a Negative Regulator of the AKT Signaling Pathway.Neoplasia. 2019 Jan;21(1):30-40. doi: 10.1016/j.neo.2018.10.009. Epub 2018 Nov 27.
• [3] Genetic analysis identifies putative tumor suppressor sites at 2q35-q36.1 and 2q36.3-q37.1 involved in cervical cancer progression.Oncogene. 2003 May 29;22(22):3489-99. doi: 10.1038/sj.onc.1206432.
• [4] 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.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [12] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [13] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [14] 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.
• [15] 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.
• [16] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.