Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTU2IC5O)

• DOT Name: Oxysterol-binding protein-related protein 11 (OSBPL11)
• Synonyms: ORP-11; OSBP-related protein 11
• Gene Name: OSBPL11
• Related Disease:
  Hepatocellular carcinoma
  Cardiovascular disease
  Obesity
• UniProt ID: OSB11_HUMAN
• PDB ID: 2D9X
• Pfam ID: PF01237 ; PF00169
• Sequence:
  MQGGEPVSTMKVSESEGKLEGQATAVTPNKNSSCGGGISSSSSSRGGSAKGWQYSDHMEN
  VYGYLMKYTNLVTGWQYRFFVLNNEAGLLEYFVNEQSRNQKPRGTLQLAGAVISPSDEDS
  HTFTVNAASGEQYKLRATDAKERQHWVSRLQICTQHHTEAIGKNNPPLKSRSFSLASSSN
  SPISQRRPSQNAISFFNVGHSKLQSLSKRTNLPPDHLVEVREMMSHAEGQQRDLIRRIEC
  LPTSGHLSSLDQDLLMLKATSMATMNCLNDCFHILQLQHASHQKGSLPSGTTIEWLEPKI
  SLSNHYKNGADQPFATDQSKPVAVPEEQPVAESGLLAREPEEINADDEIEDTCDHKEDDL
  GAVEEQRSVILHLLSQLKLGMDLTRVVLPTFILEKRSLLEMYADFMSHPDLFIAITNGAT
  AEDRMIRFVEYYLTSFHEGRKGAIAKKPYNPIIGETFHCSWKMPKSEVASSVFSSSSTQG
  VTNHAPLSGESLTQVGSDCYTVRFVAEQVSHHPPVSGFYAECTERKMCVNAHVWTKSKFL
  GMSIGVTMVGEGILSLLEHGEEYTFSLPCAYARSILTVPWVELGGKVSVNCAKTGYSASI
  TFHTKPFYGGKLHRVTAEVKHNITNTVVCRVQGEWNSVLEFTYSNGETKYVDLTKLAVTK
  KRVRPLEKQDPFESRRLWKNVTDSLRESEIDKATEHKHTLEERQRTEERHRTETGTPWKT
  KYFIKEGDGWVYHKPLWKIIPTTQPAE
• Function: Plays a role in regulating ADIPOQ and FABP4 levels in differentiating adipocytes and is also involved in regulation of adipocyte triglyceride storage. Weakly binds 25-hydroxycholesterol.
• Tissue Specificity: Present at highest levels in ovary, testis, kidney, liver, stomach, brain, and adipose tissue. Strong expression (at protein level) in epithelial cells of kidney tubules, testicular tubules, caecum, and skin . Present at low levels in subcutaneous and visceral adipose tissue (at protein level).
• Reactome Pathway: RHOH GTPase cycle (R-HSA-9013407)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Definitive	Altered Expression	[1]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[2]
Obesity	DIS47Y1K	Strong	Genetic Variation	[2]

9 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 Oxysterol-binding protein-related protein 11 (OSBPL11).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Oxysterol-binding protein-related protein 11 (OSBPL11).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Oxysterol-binding protein-related protein 11 (OSBPL11).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Oxysterol-binding protein-related protein 11 (OSBPL11).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Oxysterol-binding protein-related protein 11 (OSBPL11).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Oxysterol-binding protein-related protein 11 (OSBPL11).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Oxysterol-binding protein-related protein 11 (OSBPL11).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Oxysterol-binding protein-related protein 11 (OSBPL11).	[12]
Okadaic acid	DM47CO1	Investigative	Okadaic acid increases the expression of Oxysterol-binding protein-related protein 11 (OSBPL11).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Oxysterol-binding protein-related protein 11 (OSBPL11).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Oxysterol-binding protein-related protein 11 (OSBPL11).	[11]

References

• [1] Serum and tissue proteomic signatures of patients with hepatocellular carcinoma using 2D gel electrophoresis.Mol Med Rep. 2019 Aug;20(2):1025-1038. doi: 10.3892/mmr.2019.10311. Epub 2019 May 29.
• [2] Association of OSBPL11 gene polymorphisms with cardiovascular disease risk factors in obesity.Obesity (Silver Spring). 2009 Jul;17(7):1466-72. doi: 10.1038/oby.2009.71. Epub 2009 Mar 26.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [12] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [13] Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.