Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVH6BND)

• DOT Name: Protein phosphatase 1 regulatory subunit 1C (PPP1R1C)
• Synonyms: Inhibitor-5 of protein phosphatase 1; IPP5
• Gene Name: PPP1R1C
• Related Disease:
  Adult glioblastoma
  Cervical carcinoma
  Glioblastoma multiforme
  Neoplasm
• UniProt ID: PPR1C_HUMAN
• Pfam ID: PF05395
• Sequence:
  MEPNSPKKIQFAVPVFQSQIAPEAAEQIRKRRPTPASLVILNEHNPPEIDDKRGPNTQGE
  LQNASPKQRKQSVYTPPTIKGVKHLKGQNESAFPEEEEGTNEREEQRDH
• Function: May increase cell susceptibility to TNF-induced apoptosis.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[1]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[2]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[3]

9 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 phosphatase 1 regulatory subunit 1C (PPP1R1C).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[9]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[13]

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 Protein phosphatase 1 regulatory subunit 1C (PPP1R1C).	[11]

References

• [1] MicroRNA-182 targets protein phosphatase 1 regulatory inhibitor subunit 1C in glioblastoma.Oncotarget. 2017 Sep 27;8(70):114677-114684. doi: 10.18632/oncotarget.21309. eCollection 2017 Dec 29.
• [2] 8-60hIPP5(m)-induced G2/M cell cycle arrest involves activation of ATM/p53/p21(cip1/waf1) pathways and delayed cyclin B1 nuclear translocation.Asian Pac J Cancer Prev. 2014;15(9):4101-7. doi: 10.7314/apjcp.2014.15.9.4101.
• [3] IPP5, a novel inhibitor of protein phosphatase 1, suppresses tumor growth and progression of cervical carcinoma cells by inducing G2/M arrest.Cancer Genet. 2012 Sep;205(9):442-52. doi: 10.1016/j.cancergen.2012.06.002.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] 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.
• [10] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [11] 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.
• [12] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [13] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.