Details of Drug Off-Target (DOT)

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

• DOT Name: Platelet-derived growth factor receptor-like protein (PDGFRL)
• Synonyms: PDGFR-like protein; PDGF receptor beta-like tumor suppressor
• Gene Name: PDGFRL
• Related Disease:
  Adenocarcinoma
  Behcet disease
  Carcinoma
  Colorectal carcinoma
  Malignant peripheral nerve sheath tumor
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Squamous cell carcinoma
  Adult hepatocellular carcinoma
  Advanced cancer
• UniProt ID: PGFRL_HUMAN
• Pfam ID: PF13927 ; PF21339
• Sequence:
  MKVWLLLGLLLVHEALEDVTGQHLPKNKRPKEPGENRIKPTNKKVKPKIPKMKDRDSANS
  APKTQSIMMQVLDKGRFQKPAATLSLLAGQTVELRCKGSRIGWSYPAYLDTFKDSRLSVK
  QNERYGQLTLVNSTSADTGEFSCWVQLCSGYICRKDEAKTGSTYIFFTEKGELFVPSPSY
  FDVVYLNPDRQAVVPCRVTVLSAKVTLHREFPAKEIPANGTDIVYDMKRGFVYLQPHSEH
  QGVVYCRAEAGGRSQISVKYQLLYVAVPSGPPSTTILASSNKVKSGDDISVLCTVLGEPD
  VEVEFTWIFPGQKDERPVTIQDTWRLIHRGLGHTTRISQSVITVEDFETIDAGYYICTAQ
  NLQGQTTVATTVEFS
• Tissue Specificity: Expressed in colon, lung and liver.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Behcet disease	DISSYMBS	Strong	Genetic Variation	[2]
Carcinoma	DISH9F1N	Strong	Posttranslational Modification	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Genetic Variation	[5]
Neoplasm	DISZKGEW	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[7]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[7]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[1]
Adult hepatocellular carcinoma	DIS6ZPAI	Limited	Genetic Variation	[8]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[4]

19 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 Platelet-derived growth factor receptor-like protein (PDGFRL).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[13]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[14]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[17]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[18]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[19]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[20]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[22]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[25]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[27]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Platelet-derived growth factor receptor-like protein (PDGFRL).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Platelet-derived growth factor receptor-like protein (PDGFRL).	[26]

References

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• [2] Genetic variant on PDGFRL associated with Behet disease in Chinese Han populations.Hum Mutat. 2013 Jan;34(1):74-8. doi: 10.1002/humu.22208. Epub 2012 Oct 11.
• [3] Isolation of a candidate tumor suppressor gene on chromosome 8p21.3-p22 that is homologous to an extracellular domain of the PDGF receptor beta gene.Oncogene. 1995 Mar 2;10(5):891-5.
• [4] Expression and functional characterization of platelet-derived growth factor receptor-like gene.World J Gastroenterol. 2010 Mar 28;16(12):1465-72. doi: 10.3748/wjg.v16.i12.1465.
• [5] Microarray-based copy number analysis of neurofibromatosis type-1 (NF1)-associated malignant peripheral nerve sheath tumors reveals a role for Rho-GTPase pathway genes in NF1 tumorigenesis.Hum Mutat. 2012 Apr;33(4):763-76. doi: 10.1002/humu.22044. Epub 2012 Mar 5.
• [6] A Tumor Suppressor Gene Product, Platelet-Derived Growth Factor Receptor-Like Protein Controls Chondrocyte Proliferation and Differentiation.J Cell Biochem. 2017 Nov;118(11):4033-4044. doi: 10.1002/jcb.26059. Epub 2017 May 23.
• [7] PRLTS gene alterations in human prostate cancer.Jpn J Cancer Res. 1997 Apr;88(4):389-93. doi: 10.1111/j.1349-7006.1997.tb00394.x.
• [8] Loss of heterozygosity of chromosome 8p and 11p in the dysplastic nodule and hepatocellular carcinoma.J Gastroenterol Hepatol. 2003 Apr;18(4):430-6. doi: 10.1046/j.1440-1746.2003.02997.x.
• [9] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [15] 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.
• [16] 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.
• [17] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [18] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [19] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [20] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [21] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [22] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [23] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [24] 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.
• [25] 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.
• [26] 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.
• [27] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.