Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNM6T78)

• DOT Name: Phosphatidylinositol transfer protein beta isoform (PITPNB)
• Synonyms: PI-TP-beta; PtdIns transfer protein beta; PtdInsTP beta
• Gene Name: PITPNB
• Related Disease:
  Breast carcinoma
  Estrogen-receptor positive breast cancer
• UniProt ID: PIPNB_HUMAN
• Pfam ID: PF02121
• Sequence:
  MVLIKEFRVVLPCSVQEYQVGQLYSVAEASKNETGGGEGIEVLKNEPYEKDGEKGQYTHK
  IYHLKSKVPAFVRMIAPEGSLVFHEKAWNAYPYCRTIVTNEYMKDDFFIKIETWHKPDLG
  TLENVHGLDPNTWKTVEIVHIDIADRSQVEPADYKADEDPALFQSVKTKRGPLGPNWKKE
  LANSPDCPQMCAYKLVTIKFKWWGLQSKVENFIQKQEKRIFTNFHRQLFCWIDKWIDLTM
  EDIRRMEDETQKELETMRKRGSVRGTSAADV
• Function: Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes. Also catalyzes the transfer of sphingomyelin. Required for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum; phosphatidylinositol and phosphatidylcholine transfer activity is essential for this function.
• Tissue Specificity: Widely expressed in various tissues including brain.
• Reactome Pathway: PI and PC transport between ER and Golgi membranes (R-HSA-1483196)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[1]
Estrogen-receptor positive breast cancer	DIS1H502	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[10]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[11]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[12]
Aminoglutethimide	DMWFHMZ	Approved	Aminoglutethimide increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[13]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[16]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[17]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[18]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[19]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Phosphatidylinositol transfer protein beta isoform (PITPNB).	[20]

References

• [1] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [2] Genome-wide association study of germline variants and breast cancer-specific mortality.Br J Cancer. 2019 Mar;120(6):647-657. doi: 10.1038/s41416-019-0393-x. Epub 2019 Feb 21.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [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] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] Identification of potential biomarkers for predicting acute dermal irritation by proteomic analysis. J Appl Toxicol. 2011 Nov;31(8):762-72.
• [12] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [13] Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: role of myeloperoxidase and arylamine free radicals. Chem Biol Interact. 2015 Sep 5;239:129-38.
• [14] Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP. Toxicology. 2021 Jan 30;448:152652. doi: 10.1016/j.tox.2020.152652. Epub 2020 Dec 2.
• [15] 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.
• [16] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [17] Lipid Rafts Disruption Increases Ochratoxin A Cytotoxicity to Hepatocytes. J Biochem Mol Toxicol. 2016 Feb;30(2):71-9. doi: 10.1002/jbt.21738. Epub 2015 Aug 25.
• [18] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [19] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [20] Early gene response in lithium chloride induced apoptosis. Apoptosis. 2005 Jan;10(1):75-90. doi: 10.1007/s10495-005-6063-x.