Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUU2X2Q)

• DOT Name: Oxysterol-binding protein-related protein 7 (OSBPL7)
• Synonyms: ORP-7; OSBP-related protein 7
• Gene Name: OSBPL7
• Related Disease:
  Congenital contractural arachnodactyly
  Neoplasm
  Non-insulin dependent diabetes
• UniProt ID: OSBL7_HUMAN
• Pfam ID: PF01237 ; PF15409
• Sequence:
  MDFQERDPPFLPESAQSSKPSSAQQASELWEVVEEPRVRLGTEGVMPERQEGHLLKKRKW
  PLKGWHKRYFVLEDGILHYATTRQDITKGKLHGSIDVRLSVMSINKKAQRIDLDTEDNIY
  HLKIKSQDLFQSWVAQLRAHRLAHRLDMPRGSLPSTAHRKVPGAQLPTAATASALPGLGP
  REKVSSWLRDSDGLDRCSHELSECQGKLQELHRLLQSLESLHRIPSAPVIPTHQASVTTE
  RPKKGKRTSRMWCTQSFAKDDTIGRVGRLHGSVPNLSRYLESRDSSGTRGLPPTDYAHLQ
  RSFWALAQKVHSSLSSVLAALTMERDQLRDMHQGSELSRMGVSEASTGQRRLHSLSTSSD
  TTADSFSSLNPEEQEALYMKGRELTPQLSQTSILSLADSHTEFFDACEVLLSASSSENEG
  SEEEESCTSEITTSLSEEMLDLRGAERCQKGGCVPGRPMGPPRRRCLPAASGPGADVSLW
  NILRNNIGKDLSKVSMPVQLNEPLNTLQRLCEELEYSSLLDQASRIADPCERMVYIAAFA
  VSAYSSTYHRAGCKPFNPVLGETYECERPDRGFRFISEQVSHHPPISACHAESENFAFWQ
  DMKWKNKFWGKSLEIVPVGTVNVSLPRFGDHFEWNKVTSCIHNVLSGQRWIEHYGEVLIR
  NTQDSSCHCKITFCKAKYWSSNVHEVQGAVLSRSGRVLHRLFGKWHEGLYRGPTPGGQCI
  WKPNSMPPDHERNFGFTQFALELNELTAELKRSLPSTDTRLRPDQRYLEEGNIQAAEAQK
  RRIEQLQRDRRKVMEENNIVHQARFFRRQTDSSGKEWWVTNNTYWRLRAEPGYGNMDGAV
  LW
• Tissue Specificity: Expressed in epithelium of small and large intestines (at protein level). Expressed in stomach, duodenum, jejunum, ascending colon, spleen, thymus, lymph node, trachea and leukocytes.
• Reactome Pathway: Synthesis of bile acids and bile salts (R-HSA-192105)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital contractural arachnodactyly	DISOM1K7	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Oxysterol-binding protein-related protein 7 (OSBPL7).	[12]

1 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 7 (OSBPL7).	[9]

References

• [1] 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.
• [2] Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.Nat Commun. 2018 Jul 27;9(1):2941. doi: 10.1038/s41467-018-04951-w.
• [3] 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.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Comparative effects of raloxifene, tamoxifen and estradiol on human osteoblasts in vitro: estrogen receptor dependent or independent pathways of raloxifene. J Steroid Biochem Mol Biol. 2009 Feb;113(3-5):281-9.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [12] 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.