Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ3HGTC)

• DOT Name: Apolipoprotein A-II (APOA2)
• Synonyms: Apo-AII; ApoA-II; Apolipoprotein A2
• Gene Name: APOA2
• Related Disease: Apolipoprotein A-II amyloidosis
• UniProt ID: APOA2_HUMAN
• Pfam ID: PF04711
• Sequence:
  MKLLAATVLLLTICSLEGALVRRQAKEPCVESLVSQYFQTVTDYGKDLMEKVKSPELQAE
  AKSYFEKSKEQLTPLIKKAGTELVNFLSYFVELGTQPATQ
• Function: May stabilize HDL (high density lipoprotein) structure by its association with lipids, and affect the HDL metabolism.
• Tissue Specificity: Plasma; synthesized in the liver and intestine.
• KEGG Pathway:
  PPAR sig.ling pathway (hsa03320)
  Cholesterol metabolism (hsa04979)
• Reactome Pathway:
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Post-translational protein phosphorylation (R-HSA-8957275)
  Chylomicron assembly (R-HSA-8963888)
  Chylomicron remodeling (R-HSA-8963901)
  Retinoid metabolism and transport (R-HSA-975634)
  PPARA activates gene expression (R-HSA-1989781)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Apolipoprotein A-II amyloidosis	DIS5XAA6	Supportive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Apolipoprotein A-II (APOA2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Apolipoprotein A-II (APOA2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Apolipoprotein A-II (APOA2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Apolipoprotein A-II (APOA2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Apolipoprotein A-II (APOA2).	[6]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Apolipoprotein A-II (APOA2).	[7]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Apolipoprotein A-II (APOA2).	[8]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Apolipoprotein A-II (APOA2).	[4]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Apolipoprotein A-II (APOA2).	[4]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Apolipoprotein A-II (APOA2).	[9]
Nifedipine	DMSVOZT	Approved	Nifedipine increases the expression of Apolipoprotein A-II (APOA2).	[10]
Atenolol	DMNKG1Z	Approved	Atenolol decreases the expression of Apolipoprotein A-II (APOA2).	[11]
Clonidine	DM6RZ9Q	Approved	Clonidine decreases the expression of Apolipoprotein A-II (APOA2).	[11]
Cyproterone acetate	DMLMOIJ	Phase 4	Cyproterone acetate affects the expression of Apolipoprotein A-II (APOA2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Apolipoprotein A-II (APOA2).	[13]
LG100268	DM41RK2	Discontinued in Phase 1	LG100268 increases the expression of Apolipoprotein A-II (APOA2).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Apolipoprotein A-II (APOA2).	[14]

References

• [1] A new human hereditary amyloidosis: the result of a stop-codon mutation in the apolipoprotein AII gene. Genomics. 2001 Mar 15;72(3):272-7. doi: 10.1006/geno.2000.6499.
• [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] Retinoids increase human apolipoprotein A-11 expression through activation of the retinoid X receptor but not the retinoic acid receptor. Mol Cell Biol. 1996 Jul;16(7):3350-60. doi: 10.1128/MCB.16.7.3350.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [8] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [9] Effect of bezafibrate on lipids, lipoproteins, apolipoproteins and platelet aggregation in hypertriglyceridemic patients. Arzneimittelforschung. 1994 Nov;44(11):1217-22.
• [10] Effects of nifedipine GITS and atenolol monotherapy on serum lipids, blood pressure, heart rate, and weight in mild to moderate hypertension. Angiology. 1991 Sep;42(9):681-90. doi: 10.1177/000331979104200901.
• [11] The effects of clonidine hydrochloride versus atenolol monotherapy on serum lipids, lipid subfractions, and apolipoproteins in mild hypertension. Am Heart J. 1990 Jul;120(1):172-9. doi: 10.1016/0002-8703(90)90175-w.
• [12] Antiandrogenic therapy can cause coronary arterial disease. Int J Urol. 2005 Oct;12(10):886-91. doi: 10.1111/j.1442-2042.2005.01145.x.
• [13] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [14] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.