Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT12S5QS)

• DOT Name: Apolipoprotein F (APOF)
• Synonyms: Apo-F; Lipid transfer inhibitor protein; LTIP
• Gene Name: APOF
• Related Disease:
  Alzheimer disease
  Cardiac failure
  Congestive heart failure
  Hepatocellular carcinoma
  Hyperlipidemia
  Non-alcoholic fatty liver disease
• UniProt ID: APOF_HUMAN
• Pfam ID: PF15148
• Sequence:
  MTGLCGYSAPDMRGLRLIMIPVELLLCYLLLHPVDATSYGKQTNVLMHFPLSLESQTPSS
  DPLSCQFLHPKSLPGFSHMAPLPKFLVSLALRNALEEAGCQADVWALQLQLYRQGGVNAT
  QVLIQHLRGLQKGRSTERNVSVEALASALQLLAREQQSTGRVGRSLPTEDCENEKEQAVH
  NVVQLLPGVGTFYNLGTALYYATQNCLGKARERGRDGAIDLGYDLLMTMAGMSGGPMGLA
  ISAALKPALRSGVQQLIQYYQDQKDANISQPETTKEGLRAISDVSDLEETTTLASFISEV
  VSSAPYWGWAIIKSYDLDPGAGSLEI
• Function: Minor apolipoprotein that associates with LDL. Inhibits cholesteryl ester transfer protein (CETP) activity and appears to be an important regulator of cholesterol transport. Also associates to a lesser degree with VLDL, Apo-AI and Apo-AII.
• Tissue Specificity: Expressed by the liver and secreted in plasma.
• Reactome Pathway: LDL remodeling (R-HSA-8964041)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Cardiac failure	DISDC067	Strong	Biomarker	[2]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[4]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[5]

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 Apolipoprotein F (APOF).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Apolipoprotein F (APOF).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Apolipoprotein F (APOF).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Apolipoprotein F (APOF).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Apolipoprotein F (APOF).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Apolipoprotein F (APOF).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Apolipoprotein F (APOF).	[11]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Apolipoprotein F (APOF).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Apolipoprotein F (APOF).	[3]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Apolipoprotein F (APOF).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Apolipoprotein F (APOF).	[15]

References

• [1] Exclusion of CYP46 and APOM as candidate genes for Alzheimer's disease in a French population.Neurosci Lett. 2004 Jun 10;363(2):139-43. doi: 10.1016/j.neulet.2004.03.066.
• [2] Glycoproteomic Profiling Provides Candidate Myocardial Infarction Predictors of Later Progression to Heart Failure.ACS Omega. 2019 Jan 31;4(1):1272-1280. doi: 10.1021/acsomega.8b02207. Epub 2019 Jan 15.
• [3] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [4] Molecular cloning of hamster lipid transfer inhibitor protein (apolipoprotein F) and regulation of its expression by hyperlipidemia.J Lipid Res. 2009 Apr;50(4):676-84. doi: 10.1194/jlr.M800429-JLR200. Epub 2008 Nov 13.
• [5] Absolute quantitation of disease protein biomarkers in a single LC-MS acquisition using apolipoprotein F as an example.Sci Rep. 2017 Sep 21;7(1):12072. doi: 10.1038/s41598-017-12229-2.
• [6] 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.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] 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.
• [11] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [12] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] 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.