Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT64TTGC)

• DOT Name: Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1)
• Synonyms: Mammalian rdgB homolog beta; M-rdgB beta; MrdgBbeta; Retinal degeneration B homolog beta; RdgBbeta
• Gene Name: PITPNC1
• Related Disease:
  Asthma
  Gastric cancer
  Non-insulin dependent diabetes
  Stomach cancer
• UniProt ID: PITC1_HUMAN
• Pfam ID: PF02121
• Sequence:
  MLLKEYRICMPLTVDEYKIGQLYMISKHSHEQSDRGEGVEVVQNEPFEDPHHGNGQFTEK
  RVYLNSKLPSWARAVVPKIFYVTEKAWNYYPYTITEYTCSFLPKFSIHIETKYEDNKGSN
  DTIFDNEAKDVEREVCFIDIACDEIPERYYKESEDPKHFKSEKTGRGQLREGWRDSHQPI
  MCSYKLVTVKFEVWGLQTRVEQFVHKVVRDILLIGHRQAFAWVDEWYDMTMDEVREFERA
  TQEATNKKIGIFPPAISISSIPLLPSSVRSAPSSAPSTPLSTDAPEFLSVPKDRPRKKSA
  PETLTLPDPEKKATLNLPGMHSSDKPCRPKSE
• Function: [Isoform 1]: Catalyzes the transfer of phosphatidylinositol (PI) and phosphatidic acid (PA) between membranes. Binds PA derived from the phospholipase D signaling pathway and among the cellular PA species, preferably binds to the C16:0/16:1 and C16:1/18:1 PA species ; [Isoform 2]: Catalyzes the transfer of phosphatidylinositol between membranes.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	moderate	Genetic Variation	[1]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[2]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[3]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1) affects the response to substance of DTI-015.	[26]

3 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 Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[12]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[23]

19 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 Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin affects the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[16]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[17]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[21]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[22]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[24]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1).	[25]

References

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• [2] Adipocytes fuel gastric cancer omental metastasis via PITPNC1-mediated fatty acid metabolic reprogramming.Theranostics. 2018 Oct 29;8(19):5452-5468. doi: 10.7150/thno.28219. eCollection 2018.
• [3] Integrating genetic association, genetics of gene expression, and single nucleotide polymorphism set analysis to identify susceptibility Loci for type 2 diabetes mellitus.Am J Epidemiol. 2012 Sep 1;176(5):423-30. doi: 10.1093/aje/kws123. Epub 2012 Aug 2.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] 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.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [12] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] 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.
• [14] 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.
• [15] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [16] Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment. Cancer Biol Ther. 2008 Oct;7(10):1607-18.
• [17] The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
• [18] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [19] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [20] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [21] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [22] 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.
• [23] 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.
• [24] 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.
• [25] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [26] Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.