Details of Drug Off-Target (DOT)

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

• DOT Name: PDZ and LIM domain protein 2 (PDLIM2)
• Synonyms: PDZ-LIM protein mystique
• Gene Name: PDLIM2
• Related Disease:
  Castration-resistant prostate carcinoma
  Prostate cancer
  Prostate carcinoma
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Anaplastic large cell lymphoma
  Autoimmune disease
  Bladder cancer
  Colorectal carcinoma
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Human T-lymphotropic virus 1 infectious disease
  Lung cancer
  Lung carcinoma
  Ovarian cancer
  Ovarian neoplasm
  Urinary bladder cancer
  Urinary bladder neoplasm
  Meningioma
  Schwannoma
  Breast cancer
  Breast carcinoma
  Focal segmental glomerulosclerosis
  Membranous glomerulonephritis
  Neoplasm
  Triple negative breast cancer
• UniProt ID: PDLI2_HUMAN
• PDB ID: 2PA1; 3PDV
• Pfam ID: PF15936 ; PF00412 ; PF00595
• Sequence:
  MALTVDVAGPAPWGFRITGGRDFHTPIMVTKVAERGKAKDADLRPGDIIVAINGESAEGM
  LHAEAQSKIRQSPSPLRLQLDRSQATSPGQTNGDSSLEVLATRFQGSVRTYTESQSSLRS
  SYSSPTSLSPRAGSPFSPPPSSSSLTGEAAISRSFQSLACSPGLPAADRLSYSGRPGSRQ
  AGLGRAGDSAVLVLPPSPGPRSSRPSMDSEGGSLLLDEDSEVFKMLQENREGRAAPRQSS
  SFRLLQEALEAEERGGTPAFLPSSLSPQSSLPASRALATPPKLHTCEKCSTSIANQAVRI
  QEGRYRHPGCYTCADCGLNLKMRGHFWVGDELYCEKHARQRYSAPATLSSRA
• Function: Probable adapter protein located at the actin cytoskeleton that promotes cell attachment. Necessary for the migratory capacity of epithelial cells. Overexpression enhances cell adhesion to collagen and fibronectin and suppresses anchorage independent growth. May contribute to tumor cell migratory capacity.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Castration-resistant prostate carcinoma	DISVGAE6	Definitive	Biomarker	[1]
Prostate cancer	DISF190Y	Definitive	Biomarker	[1]
Prostate carcinoma	DISMJPLE	Definitive	Biomarker	[1]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Anaplastic large cell lymphoma	DISP4D1R	Strong	Altered Expression	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Bladder cancer	DISUHNM0	Strong	Posttranslational Modification	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[9]
Human T-lymphotropic virus 1 infectious disease	DISN5C4M	Strong	Genetic Variation	[2]
Lung cancer	DISCM4YA	Strong	Altered Expression	[10]
Lung carcinoma	DISTR26C	Strong	Biomarker	[10]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[8]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[8]
Urinary bladder cancer	DISDV4T7	Strong	Posttranslational Modification	[6]
Urinary bladder neoplasm	DIS7HACE	Strong	Posttranslational Modification	[6]
Meningioma	DISPT4TG	moderate	Biomarker	[11]
Schwannoma	DISTTVLA	moderate	Biomarker	[11]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[12]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[12]
Focal segmental glomerulosclerosis	DISJNHH0	Limited	Altered Expression	[13]
Membranous glomerulonephritis	DISFSUKQ	Limited	Altered Expression	[13]
Neoplasm	DISZKGEW	Limited	Biomarker	[12]
Triple negative breast cancer	DISAMG6N	Limited	Biomarker	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[16]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[17]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[17]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[18]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[22]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 decreases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[18]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of PDZ and LIM domain protein 2 (PDLIM2).	[24]

3 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 decreases the methylation of PDZ and LIM domain protein 2 (PDLIM2).	[21]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of PDZ and LIM domain protein 2 (PDLIM2).	[23]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of PDZ and LIM domain protein 2 (PDLIM2).	[23]

References

• [1] PDLIM2 suppression efficiently reduces tumor growth and invasiveness of human castration-resistant prostate cancer-like cells.Prostate. 2016 Feb 15;76(3):273-85. doi: 10.1002/pros.23118. Epub 2015 Oct 26.
• [2] PDLIM2 suppresses human T-cell leukemia virus type I Tax-mediated tumorigenesis by targeting Tax into the nuclear matrix for proteasomal degradation.Blood. 2009 Apr 30;113(18):4370-80. doi: 10.1182/blood-2008-10-185660. Epub 2009 Jan 8.
• [3] Pull-down Assay on Streptavidin Beads and Surface Plasmon Resonance Chips for SWATH-MS-based Interactomics.Cancer Genomics Proteomics. 2018 Sep-Oct;15(5):395-404. doi: 10.21873/cgp.20098.
• [4] Inactivation of the putative ubiquitin-E3 ligase PDLIM2 in classical Hodgkin and anaplastic large cell lymphoma.Leukemia. 2017 Mar;31(3):602-613. doi: 10.1038/leu.2016.238. Epub 2016 Aug 19.
• [5] PDLIM2 inhibits T helper 17 cell development and granulomatous inflammation through degradation of STAT3.Sci Signal. 2011 Dec 6;4(202):ra85. doi: 10.1126/scisignal.2001637.
• [6] Construction of a recombinant eukaryotic expression plasmid containing human PDLIM2 gene and its biological activity.Plasmid. 2011 Jul;66(2):106-11. doi: 10.1016/j.plasmid.2011.06.005. Epub 2011 Jul 19.
• [7] A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NFB and STAT3 in colorectal cancer cells.Gastroenterology. 2014 Oct;147(4):847-859.e11. doi: 10.1053/j.gastro.2014.06.006. Epub 2014 Jun 12.
• [8] Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling.Oncotarget. 2016 Jan 12;7(2):1408-20. doi: 10.18632/oncotarget.6368.
• [9] Systematic profiling identifies PDLIM2 as a novel prognostic predictor for oesophageal squamous cell carcinoma (ESCC).J Cell Mol Med. 2019 Aug;23(8):5751-5761. doi: 10.1111/jcmm.14491. Epub 2019 Jun 20.
• [10] Causative role of PDLIM2 epigenetic repression in lung cancer and therapeutic resistance.Nat Commun. 2019 Nov 22;10(1):5324. doi: 10.1038/s41467-019-13331-x.
• [11] Global Proteome and Phospho-proteome Analysis of Merlin-deficient Meningioma and Schwannoma Identifies PDLIM2 as a Novel Therapeutic Target.EBioMedicine. 2017 Feb;16:76-86. doi: 10.1016/j.ebiom.2017.01.020. Epub 2017 Jan 18.
• [12] PDLIM2 Is a Marker of Adhesion and -Catenin Activity in Triple-Negative Breast Cancer.Cancer Res. 2019 May 15;79(10):2619-2633. doi: 10.1158/0008-5472.CAN-18-2787. Epub 2019 Mar 18.
• [13] Pdlim2 is a novel actin-regulating protein of podocyte foot processes.Kidney Int. 2011 Nov;80(10):1045-54. doi: 10.1038/ki.2011.231. Epub 2011 Aug 3.
• [14] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [15] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [16] 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.
• [17] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [18] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [19] 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.
• [20] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [21] 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.
• [22] 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.
• [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] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.