Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8QBVTY)

• DOT Name: Apolipoprotein L1 (APOL1)
• Synonyms: Apolipoprotein L; Apo-L; ApoL; Apolipoprotein L-I; ApoL-I
• Gene Name: APOL1
• Related Disease: Focal segmental glomerulosclerosis 4, susceptibility to
• UniProt ID: APOL1_HUMAN
• PDB ID: 7L6K; 7LF7; 7LFA; 7LFB; 7LFD
• Pfam ID: PF05461
• Sequence:
  MEGAALLRVSVLCIWMSALFLGVGVRAEEAGARVQQNVPSGTDTGDPQSKPLGDWAAGTM
  DPESSIFIEDAIKYFKEKVSTQNLLLLLTDNEAWNGFVAAAELPRNEADELRKALDNLAR
  QMIMKDKNWHDKGQQYRNWFLKEFPRLKSELEDNIRRLRALADGVQKVHKGTTIANVVSG
  SLSISSGILTLVGMGLAPFTEGGSLVLLEPGMELGITAALTGITSSTMDYGKKWWTQAQA
  HDLVIKSLDKLKEVREFLGENISNFLSLAGNTYQLTRGIGKDIRALRRARANLQSVPHAS
  ASRPRVTEPISAESGEQVERVNEPSILEMSRGVKLTDVAPVSFFLVLDVVYLVYESKHLH
  EGAKSETAEELKKVAQELEEKLNILNNNYKILQADQEL
• Function: May play a role in lipid exchange and transport throughout the body. May participate in reverse cholesterol transport from peripheral cells to the liver.
• Tissue Specificity: Plasma. Found on APOA-I-containing high density lipoprotein (HDL3). Expressed in pancreas, lung, prostate, liver, placenta and spleen.
• KEGG Pathway: African trypanosomiasis (hsa05143)
• 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)
  Scavenging of heme from plasma (R-HSA-2168880)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Focal segmental glomerulosclerosis 4, susceptibility to	DIS80WYW	Definitive	Autosomal recessive	[1]

19 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 L1 (APOL1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Apolipoprotein L1 (APOL1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Apolipoprotein L1 (APOL1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Apolipoprotein L1 (APOL1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Apolipoprotein L1 (APOL1).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Apolipoprotein L1 (APOL1).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Apolipoprotein L1 (APOL1).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Apolipoprotein L1 (APOL1).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Apolipoprotein L1 (APOL1).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Apolipoprotein L1 (APOL1).	[10]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of Apolipoprotein L1 (APOL1).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Apolipoprotein L1 (APOL1).	[12]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Apolipoprotein L1 (APOL1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Apolipoprotein L1 (APOL1).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Apolipoprotein L1 (APOL1).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Apolipoprotein L1 (APOL1).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Apolipoprotein L1 (APOL1).	[17]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Apolipoprotein L1 (APOL1).	[18]
Manganese	DMKT129	Investigative	Manganese increases the expression of Apolipoprotein L1 (APOL1).	[19]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Apolipoprotein L1 (APOL1).	[15]

References

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• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [14] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] Ochratoxin a lowers mRNA levels of genes encoding for key proteins of liver cell metabolism. Cancer Genomics Proteomics. 2008 Nov-Dec;5(6):319-32.
• [19] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.