Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLQVV22)

• DOT Name: PDZ and LIM domain protein 5 (PDLIM5)
• Synonyms: Enigma homolog; Enigma-like PDZ and LIM domains protein
• Gene Name: PDLIM5
• Related Disease:
  T-cell acute lymphoblastic leukaemia
  Adult glioblastoma
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Dilated cardiomyopathy
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Glioblastoma multiforme
  Glioma
  Hepatitis
  Hepatitis A virus infection
  Hepatocellular carcinoma
  High blood pressure
  Leukemia
  Myocardial ischemia
  Myopathy
  Nail-patella syndrome
  Nasopharyngeal carcinoma
  Neoplasm
  Non-insulin dependent diabetes
  Osteosarcoma
  Ovarian cancer
  Pancreatic cancer
  Prostate cancer
  Prostate carcinoma
  Reducing body myopathy
  Squamous cell carcinoma
  Trichohepatoenteric syndrome
  Uterine fibroids
  Coronary heart disease
  Hypertrophic cardiomyopathy
  Metastatic malignant neoplasm
  Bladder cancer
  Colorectal carcinoma
  Gastric cancer
  Lung cancer
  Lung carcinoma
  Myofibrillar myopathy
  Neuroblastoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: PDLI5_HUMAN
• PDB ID: 2DAR; 2UZC
• Pfam ID: PF00412 ; PF00595
• Sequence:
  MSNYSVSLVGPAPWGFRLQGGKDFNMPLTISSLKDGGKAAQANVRIGDVVLSIDGINAQG
  MTHLEAQNKIKGCTGSLNMTLQRASAAPKPEPVPVQKGEPKEVVKPVPITSPAVSKVTST
  NNMAYNKAPRPFGSVSSPKVTSIPSPSSAFTPAHATTSSHASPSPVAAVTPPLFAASGLH
  ANANLSADQSPSALSAGKTAVNVPRQPTVTSVCSETSQELAEGQRRGSQGDSKQQNGPPR
  KHIVERYTEFYHVPTHSDASKKRLIEDTEDWRPRTGTTQSRSFRILAQITGTEHLKESEA
  DNTKKANNSQEPSPQLASSVASTRSMPESLDSPTSGRPGVTSLTAAAAFKPVGSTGVIKS
  PSWQRPNQGVPSTGRISNSATYSGSVAPANSALGQTQPSDQDTLVQRAEHIPAGKRTPMC
  AHCNQVIRGPFLVALGKSWHPEEFNCAHCKNTMAYIGFVEEKGALYCELCYEKFFAPECG
  RCQRKILGEVISALKQTWHVSCFVCVACGKPIRNNVFHLEDGEPYCETDYYALFGTICHG
  CEFPIEAGDMFLEALGYTWHDTCFVCSVCCESLEGQTFFSKKDKPLCKKHAHSVNF
• Function: May play an important role in the heart development by scaffolding PKC to the Z-disk region. May play a role in the regulation of cardiomyocyte expansion. Isoforms lacking the LIM domains may negatively modulate the scaffolding activity of isoform 1. Overexpression promotes the development of heart hypertrophy. Contributes to the regulation of dendritic spine morphogenesis in neurons. May be required to restrain postsynaptic growth of excitatory synapses. Isoform 1, but not isoform 2, expression favors spine thinning and elongation.
• Tissue Specificity: Heart and skeletal muscle specific. Expression is commonly increased in the brain of patients with bipolar disorder, schizophrenia, and major depression.
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[4]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[4]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[9]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[10]
Hepatitis	DISXXX35	Strong	Biomarker	[11]
Hepatitis A virus infection	DISUMFQV	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[13]
Leukemia	DISNAKFL	Strong	Biomarker	[14]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[15]
Myopathy	DISOWG27	Strong	Genetic Variation	[16]
Nail-patella syndrome	DIS8C4CT	Strong	Genetic Variation	[17]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[13]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[5]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[20]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[21]
Prostate cancer	DISF190Y	Strong	Biomarker	[22]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[23]
Reducing body myopathy	DISFDWS0	Strong	Biomarker	[24]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[25]
Trichohepatoenteric syndrome	DISL3ODF	Strong	Genetic Variation	[26]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[27]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[28]
Hypertrophic cardiomyopathy	DISQG2AI	moderate	Genetic Variation	[29]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[30]
Bladder cancer	DISUHNM0	Limited	Genetic Variation	[31]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[32]
Gastric cancer	DISXGOUK	Limited	Biomarker	[33]
Lung cancer	DISCM4YA	Limited	Biomarker	[34]
Lung carcinoma	DISTR26C	Limited	Biomarker	[34]
Myofibrillar myopathy	DISF24LW	Limited	Genetic Variation	[35]
Neuroblastoma	DISVZBI4	Limited	Genetic Variation	[36]
Stomach cancer	DISKIJSX	Limited	Biomarker	[33]
Urinary bladder cancer	DISDV4T7	Limited	Genetic Variation	[31]
Urinary bladder neoplasm	DIS7HACE	Limited	Genetic Variation	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	PDZ and LIM domain protein 5 (PDLIM5) affects the response to substance of Fluorouracil.	[65]

29 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 PDZ and LIM domain protein 5 (PDLIM5).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[44]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[45]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[46]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[47]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[48]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[49]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[50]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[51]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[52]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[51]
Haloperidol	DM96SE0	Approved	Haloperidol decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[51]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[53]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[54]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[55]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[56]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[57]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[59]
NS398	DMINUWH	Terminated	NS398 increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[61]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[62]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[63]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of PDZ and LIM domain protein 5 (PDLIM5).	[64]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of PDZ and LIM domain protein 5 (PDLIM5).	[58]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of PDZ and LIM domain protein 5 (PDLIM5).	[58]

References

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