Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEZ4LOV)

• DOT Name: Proteolipid protein 2 (PLP2)
• Synonyms: Differentiation-dependent protein A4; Intestinal membrane A4 protein
• Gene Name: PLP2
• UniProt ID: PLP2_HUMAN
• Pfam ID: PF01284
• Sequence:
  MADSERLSAPGCWAACTNFSRTRKGILLFAEIILCLVILICFSASTPGYSSLSVIEMILA
  AIFFVVYMCDLHTKIPFINWPWSDFFRTLIAAILYLITSIVVLVERGNHSKIVAGVLGLI
  ATCLFGYDAYVTFPVRQPRHTAAPTDPADGPV
• Function: May play a role in cell differentiation in the intestinal epithelium.
• Tissue Specificity: Enriched in colonic mucosa. The expression of A4 follows a gradient along the crypto-villus axis with the most abundant message occurring in the lower half of the crypt.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Proteolipid protein 2 (PLP2) affects the response to substance of Cisplatin.	[17]
Fluorouracil	DMUM7HZ	Approved	Proteolipid protein 2 (PLP2) affects the response to substance of Fluorouracil.	[17]

15 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 Proteolipid protein 2 (PLP2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Proteolipid protein 2 (PLP2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Proteolipid protein 2 (PLP2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Proteolipid protein 2 (PLP2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Proteolipid protein 2 (PLP2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Proteolipid protein 2 (PLP2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Proteolipid protein 2 (PLP2).	[7]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Proteolipid protein 2 (PLP2).	[8]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Proteolipid protein 2 (PLP2).	[9]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Proteolipid protein 2 (PLP2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Proteolipid protein 2 (PLP2).	[12]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Proteolipid protein 2 (PLP2).	[14]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Proteolipid protein 2 (PLP2).	[15]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Proteolipid protein 2 (PLP2).	[16]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Proteolipid protein 2 (PLP2).	[10]

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 Proteolipid protein 2 (PLP2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Proteolipid protein 2 (PLP2).	[13]

References

• [1] 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.
• [2] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
• [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] 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.
• [13] 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.
• [14] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [15] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [16] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [17] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.