Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZS3IT6)

• DOT Name: cAMP-regulated phosphoprotein 19 (ARPP19)
• Synonyms: ARPP-19
• Gene Name: ARPP19
• Related Disease:
  Acute myelogenous leukaemia
  Alzheimer disease
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: ARP19_HUMAN
• PDB ID: 8TTB
• Pfam ID: PF04667
• Sequence:
  MSAEVPEAASAEEQKEMEDKVTSPEKAEEAKLKARYPHLGQKPGGSDFLRKRLQKGQKYF
  DSGDYNMAKAKMKNKQLPTAAPDKTEVTGDHIPTPQDLPQRKPSLVASKLAG
• Function: Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis. When phosphorylated at Ser-62 during mitosis, specifically interacts with PPP2R2D (PR55-delta) and inhibits its activity, leading to inactivation of PP2A, an essential condition to keep cyclin-B1-CDK1 activity high during M phase. May indirectly enhance GAP-43 expression.
• Reactome Pathway: MASTL Facilitates Mitotic Progression (R-HSA-2465910)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]

1 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 cAMP-regulated phosphoprotein 19 (ARPP19).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[11]
Aspirin	DM672AH	Approved	Aspirin increases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[12]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of cAMP-regulated phosphoprotein 19 (ARPP19).	[13]

References

• [1] Arpp19 Promotes Myc and Cip2a Expression and Associates with Patient Relapse in Acute Myeloid Leukemia.Cancers (Basel). 2019 Nov 11;11(11):1774. doi: 10.3390/cancers11111774.
• [2] Decreased levels of ARPP-19 and PKA in brains of Down syndrome and Alzheimer's disease.J Neural Transm Suppl. 2001;(61):263-72. doi: 10.1007/978-3-7091-6262-0_21.
• [3] Increased ARPP-19 expression is associated with hepatocellular carcinoma.Int J Mol Sci. 2014 Dec 24;16(1):178-92. doi: 10.3390/ijms16010178.
• [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] 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.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [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] 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.
• [10] Combination of arsenic trioxide and Dasatinib: a new strategy to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia. J Cell Mol Med. 2018 Mar;22(3):1614-1626.
• [11] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [12] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.