Details of Drug Off-Target (DOT)

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

• DOT Name: Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4)
• Gene Name: PPP4R4
• Related Disease: Chronic obstructive pulmonary disease
• UniProt ID: PP4R4_HUMAN
• Sequence:
  MHPPPPAAAMDFSQNSLFGYMEDLQELTIIERPVRRSLKTPEEIERLTVDEDLSDIERAV
  YLLSAGQDVQGTSVIANLPFLMRQNPTETLRRVLPKVREALHVAGVEMQLTAAMSFLTIL
  QDESVSIHAYTHSFLQVILLHLEHRDTGVSNAWLETLLSVIEVLPKETLRHEILNPLVSK
  AQLSQTVQSRLVSCKILGKLTNKFDAHTIKREILPLVKSLCQDVEYEVRSCMCRQLENIA
  QGIGTELTKSVVLPELIELSRDEGSSVRLAAFETLVNLLDIFDTDDRSQTILPLVKSFCE
  KSFKADESILISLSFHLGKLCHGLYGIFTPDQHLRFLEFYKKLCTLGLQQENGHNENQIP
  PQILEQEKKYISVRKNCAYNFPAMIVFVDPKNFHMELYSTFFCLCHDPEVPVRYTIAICF
  YEVSKLLNSGVYLIHKELITLLQDESLEVLDALIDHLPEILELMSTGGESSVQENKLSSL
  PDLIPALTAAEQRAAASLKWRTHEKLLQKYACLPHVISSDQIYYRFLQRMFTIMMTNNVL
  PVQKAASRTLCIFLRYNRKQEQRHEVIQKLIEQLGQGKSYWNRLRFLDTCEFIIEIFSKS
  FFCKYFFLPAIELTHDPVANVRMKLCYLLPKVKSTLKIPADKHLLQQLEMCVRKLLCQEK
  DKDVLAIVKRTVLELDRMEMSMDAFQKKFYEKDLLDQEKEREELLLLEMEQLEKEKQQND
  GRPMSDKMFEKKRRDTKTPTQSLPKNIPISVPGPSSVTPSTSKEIKKSKLIRSQSFNNQA
  FHAKYGNLEKCASKSSTTGYTTSVSGLGKTSVLSLADDSFRTRNASSVPSSFSPNTPLPS
  TSRGTGNSVDPKSSGSKDTQPRKATLKSRKSNP
• Function: Putative regulatory subunit of serine/threonine-protein phosphatase 4.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[1]

14 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 Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[8]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[10]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Serine/threonine-protein phosphatase 4 regulatory subunit 4 (PPP4R4).	[11]

References

• [1] Genetic Association and Risk Scores in a Chronic Obstructive Pulmonary Disease Meta-analysis of 16,707 Subjects.Am J Respir Cell Mol Biol. 2017 Jul;57(1):35-46. doi: 10.1165/rcmb.2016-0331OC.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] 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.
• [8] 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.
• [9] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.