Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDGLB4J)

• DOT Name: Oxysterol-binding protein 2 (OSBP2)
• Synonyms: Oxysterol-binding protein-related protein 4; ORP-4; OSBP-related protein 4
• Gene Name: OSBP2
• Related Disease:
  Age-related macular degeneration
  Cardiac failure
  Chronic myelomonocytic leukaemia
  Congenital contractural arachnodactyly
  Congestive heart failure
  Hepatitis C virus infection
  Methicillin-resistant staphylococci infection
  Pneumonia
• UniProt ID: OSBP2_HUMAN
• Pfam ID: PF01237 ; PF00169
• Sequence:
  MGKAAAPSRGGGCGGRSRGLSSLFTVVPCLSCHTAAPGMSASTSGSGPEPKPQPQPVPEP
  ERGPLSEQVSEAVSEAVPRSEPVSETTSEPEPGAGQPSELLQGSRPGSESSSGVGAGPFT
  KAASEPLSRAVGSATFLRPESGSLPALKPLPLLRPGQAKTPLGVPMSGTGTTSSAPLALL
  PLDSFEGWLLKWTNYLKGYQRRWFVLGNGLLSYYRNQGEMAHTCRGTINLSTAHIDTEDS
  CGILLTSGARSYHLKASSEVDRQQWITALELAKAKAVRVMNTHSDDSGDDDEATTPADKS
  ELHHTLKNLSLKLDDLSTCNDLIAKHGAALQRSLTELDGLKIPSESGEKLKVVNERATLF
  RITSNAMINACRDFLELAEIHSRKWQRALQYEQEQRVHLEETIEQLAKQHNSLERAFHSA
  PGRPANPSKSFIEGSLLTPKGEDSEEDEDTEYFDAMEDSTSFITVITEAKEDSRKAEGST
  GTSSVDWSSADNVLDGASLVPKGSSKVKRRVRIPNKPNYSLNLWSIMKNCIGRELSRIPM
  PVNFNEPLSMLQRLTEDLEYHHLLDKAVHCTSSVEQMCLVAAFSVSSYSTTVHRIAKPFN
  PMLGETFELDRLDDMGLRSLCEQVSHHPPSAAHYVFSKHGWSLWQEITISSKFRGKYISI
  MPLGAIHLEFQASGNHYVWRKSTSTVHNIIVGKLWIDQSGDIEIVNHKTNDRCQLKFLPY
  SYFSKEAARKVTGVVSDSQGKAHYVLSGSWDEQMECSKVMHSSPSSPSSDGKQKTVYQTL
  SAKLLWKKYPLPENAENMYYFSELALTLNEHEEGVAPTDSRLRPDQRLMEKGRWDEANTE
  KQRLEEKQRLSRRRRLEACGPGSSCSSEEEKEADAYTPLWFEKRLDPLTGEMACVYKGGY
  WEAKEKQDWHMCPNIF
• Function: Binds 7-ketocholesterol.
• Tissue Specificity: Expressed mainly in retina, testis, and fetal liver.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Age-related macular degeneration	DIS0XS2C	Strong	Biomarker	[1]
Cardiac failure	DISDC067	Strong	Biomarker	[2]
Chronic myelomonocytic leukaemia	DISDN5P7	Strong	Genetic Variation	[3]
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[4]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[5]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[6]
Pneumonia	DIS8EF3M	moderate	Biomarker	[6]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Gemcitabine	DMSE3I7	Approved	Oxysterol-binding protein 2 (OSBP2) increases the Neutropenia ADR of Gemcitabine.	[22]

14 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 2 (OSBP2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Oxysterol-binding protein 2 (OSBP2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Oxysterol-binding protein 2 (OSBP2).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Oxysterol-binding protein 2 (OSBP2).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Oxysterol-binding protein 2 (OSBP2).	[11]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Oxysterol-binding protein 2 (OSBP2).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Oxysterol-binding protein 2 (OSBP2).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Oxysterol-binding protein 2 (OSBP2).	[13]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Oxysterol-binding protein 2 (OSBP2).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Oxysterol-binding protein 2 (OSBP2).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Oxysterol-binding protein 2 (OSBP2).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Oxysterol-binding protein 2 (OSBP2).	[19]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Oxysterol-binding protein 2 (OSBP2).	[20]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate affects the expression of Oxysterol-binding protein 2 (OSBP2).	[21]

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 increases the methylation of Oxysterol-binding protein 2 (OSBP2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Oxysterol-binding protein 2 (OSBP2).	[17]

References

• [1] Mutation analysis of oxisterol-binding-protein gene in patients with age-related macular degeneration.Genet Test. 2007 Winter;11(4):421-6. doi: 10.1089/gte.2007.0021.
• [2] Structural and myocardial dysfunction in heart failure beyond ejection fraction.Heart Fail Rev. 2020 Jan;25(1):9-17. doi: 10.1007/s10741-019-09828-8.
• [3] Essential role of PTPN11 mutation in enhanced haematopoietic differentiation potential of induced pluripotent stem cells of juvenile myelomonocytic leukaemia.Br J Haematol. 2019 Oct;187(2):163-173. doi: 10.1111/bjh.16060. Epub 2019 Jun 20.
• [4] Expression of oxysterol binding protein isoforms in opisthorchiasis-associated cholangiocarcinoma: a potential molecular marker for tumor metastasis.Parasitol Int. 2012 Mar;61(1):136-9. doi: 10.1016/j.parint.2011.07.003. Epub 2011 Jul 8.
• [5] Inhibition of HCV replication by oxysterol-binding protein-related protein 4 (ORP4) through interaction with HCV NS5B and alteration of lipid droplet formation.PLoS One. 2013 Sep 17;8(9):e75648. doi: 10.1371/journal.pone.0075648. eCollection 2013.
• [6] Modification Targeting the "Rana Box" Motif of a Novel Nigrocin Peptide From Hylarana latouchii Enhances and Broadens Its Potency Against Multiple Bacteria.Front Microbiol. 2018 Nov 28;9:2846. doi: 10.3389/fmicb.2018.02846. eCollection 2018.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] 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.
• [10] 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.
• [11] Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):47-55. doi: 10.1016/j.mce.2004.04.010.
• [12] 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.
• [13] 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.
• [14] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [15] 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.
• [16] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [17] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [18] 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.
• [19] 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.
• [20] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [21] Gene profiles of THP-1 macrophages after in vitro exposure to respiratory (non-)sensitizing chemicals: identification of discriminating genetic markers and pathway analysis. Toxicol In Vitro. 2009 Sep;23(6):1151-62. doi: 10.1016/j.tiv.2009.06.007. Epub 2009 Jun 13.
• [22] Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan. Cancer Sci. 2013 Aug;104(8):1074-82. doi: 10.1111/cas.12186. Epub 2013 Jun 10.