Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM78ZFI)

• DOT Name: Glycolipid transfer protein (GLTP)
• Synonyms: GLTP
• Gene Name: GLTP
• Related Disease:
  Colorectal carcinoma
  Hepatitis C virus infection
  Colon carcinoma
• UniProt ID: GLTP_HUMAN
• PDB ID: 1SWX; 1SX6; 2EUK; 2EUM; 2EVD; 2EVL; 2EVS; 2EVT; 3RIC; 3RWV; 3RZN; 3S0I; 3S0K; 4GH0; 4GHP; 4GHS; 4GIX; 4GJQ; 4GVT; 4GXD; 4GXG; 4H2Z
• Pfam ID: PF08718
• Sequence:
  MALLAEHLLKPLPADKQIETGPFLEAVSHLPPFFDCLGSPVFTPIKADISGNITKIKAVY
  DTNPAKFRTLQNILEVEKEMYGAEWPKVGATLALMWLKRGLRFIQVFLQSICDGERDENH
  PNLIRVNATKAYEMALKKYHGWIVQKIFQAALYAAPYKSDFLKALSKGQNVTEEECLEKI
  RLFLVNYTATIDVIYEMYTQMNAELNYKV
• Function: Accelerates the intermembrane transfer of various glycolipids. Catalyzes the transfer of various glycosphingolipids between membranes but does not catalyze the transfer of phospholipids. May be involved in the intracellular translocation of glucosylceramides.
• Tissue Specificity: Detected in fibroblasts (at protein level). Detected in fibroblasts and in various cancer cell lines.
• Reactome Pathway: Glycosphingolipid biosynthesis (R-HSA-9840309)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[3]

8 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 Glycolipid transfer protein (GLTP).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Glycolipid transfer protein (GLTP).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Glycolipid transfer protein (GLTP).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glycolipid transfer protein (GLTP).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Glycolipid transfer protein (GLTP).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Glycolipid transfer protein (GLTP).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glycolipid transfer protein (GLTP).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Glycolipid transfer protein (GLTP).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Glycolipid transfer protein (GLTP).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Glycolipid transfer protein (GLTP).	[11]

References

• [1] MicroRNA 196B Regulates HOXA5, HOXB6 and GLTP Expression Levels in Colorectal Cancer Cells.Pathol Oncol Res. 2019 Jul;25(3):953-959. doi: 10.1007/s12253-018-0399-3. Epub 2018 Mar 12.
• [2] Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication.Acta Pharm Sin B. 2019 Jul;9(4):769-781. doi: 10.1016/j.apsb.2019.01.013. Epub 2019 Jan 29.
• [3] Upregulation of human glycolipid transfer protein (GLTP) induces necroptosis in colon carcinoma cells.Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Feb;1864(2):158-167. doi: 10.1016/j.bbalip.2018.11.002. Epub 2018 Nov 22.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 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.
• [9] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] 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.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.