Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0TFMBE)

• DOT Name: Oxysterol-binding protein-related protein 10 (OSBPL10)
• Synonyms: ORP-10; OSBP-related protein 10
• Gene Name: OSBPL10
• Related Disease:
  Hyperlipidemia, familial combined, LPL related
  Peripheral arterial disease
  Peripheral vascular disease
  Schizophrenia
  Prostate cancer
  Prostate carcinoma
• UniProt ID: OSB10_HUMAN
• Pfam ID: PF01237 ; PF15409
• Sequence:
  MERAVQGTDGGGGSNSSSRSSSRATSAGSSPSCSLAGRGVSSRSAAAGLGGGGSRSSPGS
  VAASPSGGGGRRREPALEGVLSKYTNLLQGWQNRYFVLDFEAGILQYFVNEQSKHQKPRG
  VLSLSGAIVSLSDEAPHMLVVYSANGEMFKLRAADAKEKQFWVTQLRACAKYHMEMNSKS
  APSSRSRSLTLLPHGTPNSASPCSQRHLSVGAPGVVTITHHKSPAAARRAKSQYSGQLHE
  VREMMNQVEGQQKNLVHAIESLPGSGPLTALDQDLLLLKATSAATLSCLGECLNLLQQSV
  HQAGQPSQKPGASENILGWHGSKSHSTEQLKNGTLGSLPSASANITWAILPNSAEDEQTS
  QPEPEPNSGSELVLSEDEKSDNEDKEETELGVMEDQRSIILHLISQLKLGMDLTKVVLPT
  FILEKRSLLEMYADFMAHPDLLLAITAGATPEERVICFVEYYLTAFHEGRKGALAKKPYN
  PIIGETFHCSWEVPKDRVKPKRTASRSPASCHEHPMADDPSKSYKLRFVAEQVSHHPPIS
  CFYCECEEKRLCVNTHVWTKSKFMGMSVGVSMIGEGVLRLLEHGEEYVFTLPSAYARSIL
  TIPWVELGGKVSINCAKTGYSATVIFHTKPFYGGKVHRVTAEVKHNPTNTIVCKAHGEWN
  GTLEFTYNNGETKVIDTTTLPVYPKKIRPLEKQGPMESRNLWREVTRYLRLGDIDAATEQ
  KRHLEEKQRVEERKRENLRTPWKPKYFIQEGDGWVYFNPLWKAH
• Function: Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P (Probable). Plays a role in negative regulation of lipid biosynthesis. Negatively regulates APOB secretion from hepatocytes. Binds cholesterol and acidic phospholipids. Also binds 25-hydroxycholesterol. Binds phosphatidylserine.
• Reactome Pathway: Acyl chain remodelling of PS (R-HSA-1482801)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hyperlipidemia, familial combined, LPL related	DISL1CE3	Strong	Genetic Variation	[1]
Peripheral arterial disease	DIS78WFB	Strong	Genetic Variation	[2]
Peripheral vascular disease	DISXSU1Y	Strong	Genetic Variation	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Prostate cancer	DISF190Y	Limited	Biomarker	[4]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[4]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Oxysterol-binding protein-related protein 10 (OSBPL10) affects the response to substance of Paclitaxel.	[24]
Vinblastine	DM5TVS3	Approved	Oxysterol-binding protein-related protein 10 (OSBPL10) affects the response to substance of Vinblastine.	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[17]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[18]
Testosterone Undecanoate	DMZO10Y	Approved	Testosterone Undecanoate increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[19]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[20]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[21]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Oxysterol-binding protein-related protein 10 (OSBPL10).	[23]

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 affects the phosphorylation of Oxysterol-binding protein-related protein 10 (OSBPL10).	[22]

References

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• [2] Identification of evidence suggestive of an association with peripheral arterial disease at the OSBPL10 locus by genome-wide investigation in the Japanese population.J Atheroscler Thromb. 2010 Oct 27;17(10):1054-62. doi: 10.5551/jat.4291. Epub 2010 Jul 2.
• [3] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [4] Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis.Dis Markers. 2015;2015:241301. doi: 10.1155/2015/241301. Epub 2015 Sep 28.
• [5] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [6] 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.
• [7] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [8] 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.
• [9] 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.
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• [11] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [12] 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.
• [13] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [14] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [15] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [16] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [17] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [18] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [19] Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
• [20] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [21] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [22] 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.
• [23] 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.
• [24] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.