Details of Drug Off-Target (DOT)

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

DOT Name Programmed cell death protein 10 (PDCD10)
Synonyms Cerebral cavernous malformations 3 protein; TF-1 cell apoptosis-related protein 15
Gene Name PDCD10
Related Disease
Cerebral cavernous malformation 3 ( )
Prostate cancer ( )
Prostate carcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
Bladder cancer ( )
Brain cancer ( )
Brain disease ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Cerebral cavernous malformation ( )
Cerebral cavernous malformation 1 ( )
Cerebral cavernous malformation 2 ( )
Colorectal carcinoma ( )
Glioblastoma multiforme ( )
Non-small-cell lung cancer ( )
Sezary syndrome ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Wilson disease ( )
Famililal cerebral cavernous malformations ( )
Neoplasm ( )
Abscess ( )
Nervous system disease ( )
Schistosomiasis ( )
Stroke ( )
Vascular malformation ( )
UniProt ID
PDC10_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3AJM; 3L8I; 3L8J; 3RQE; 3RQF; 3RQG; 3W8H; 3W8I; 4GEH; 4TVQ
Pfam ID
PF06840 ; PF20929
Sequence
MRMTMEEMKNEAETTSMVSMPLYAVMYPVFNELERVNLSAAQTLRAAFIKAEKENPGLTQ
DIIMKILEKKSVEVNFTESLLRMAADDVEEYMIERPEPEFQDLNEKARALKQILSKIPDE
INDRVRFLQTIKDIASAIKELLDTVNNVFKKYQYQNRRALEHQKKEFVKYSKSFSDTLKT
YFKDGKAINVFVSANRLIHQTNLILQTFKTVA
Function
Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity and STK26 activity. Important for cell migration, and for normal structure and assembly of the Golgi complex. Important for KDR/VEGFR2 signaling. Increases the stability of KDR/VEGFR2 and prevents its breakdown. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development.
Tissue Specificity Ubiquitous.
KEGG Pathway
Adherens junction (hsa04520 )

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cerebral cavernous malformation 3 DISHAV0P Definitive Autosomal dominant [1]
Prostate cancer DISF190Y Definitive Biomarker [2]
Prostate carcinoma DISMJPLE Definitive Biomarker [2]
Adult glioblastoma DISVP4LU Strong Biomarker [3]
Advanced cancer DISAT1Z9 Strong Biomarker [4]
Bladder cancer DISUHNM0 Strong Altered Expression [5]
Brain cancer DISBKFB7 Strong Genetic Variation [6]
Brain disease DIS6ZC3X Strong Genetic Variation [6]
Brain neoplasm DISY3EKS Strong Genetic Variation [6]
Breast cancer DIS7DPX1 Strong Biomarker [7]
Breast carcinoma DIS2UE88 Strong Biomarker [7]
Cerebral cavernous malformation DISLKNYA Strong Altered Expression [8]
Cerebral cavernous malformation 1 DIST5TVM Strong Genetic Variation [9]
Cerebral cavernous malformation 2 DIS7DG9B Strong Biomarker [9]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Glioblastoma multiforme DISK8246 Strong Biomarker [3]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [11]
Sezary syndrome DISFMTC7 Strong Altered Expression [12]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [5]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [5]
Wilson disease DISVS9H7 Strong Genetic Variation [13]
Famililal cerebral cavernous malformations DISP72I1 Supportive Autosomal dominant [14]
Neoplasm DISZKGEW Disputed Altered Expression [3]
Abscess DISAP982 Limited Genetic Variation [15]
Nervous system disease DISJ7GGT Limited Genetic Variation [16]
Schistosomiasis DIS6PD44 Limited Biomarker [17]
Stroke DISX6UHX Limited Genetic Variation [16]
Vascular malformation DIS2DB7A Limited Biomarker [15]
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⏷ Show the Full List of 28 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Programmed cell death protein 10 (PDCD10). [18]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Programmed cell death protein 10 (PDCD10). [19]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Programmed cell death protein 10 (PDCD10). [20]
Aspirin DM672AH Approved Aspirin increases the expression of Programmed cell death protein 10 (PDCD10). [22]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the expression of Programmed cell death protein 10 (PDCD10). [23]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Programmed cell death protein 10 (PDCD10). [24]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Programmed cell death protein 10 (PDCD10). [25]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Programmed cell death protein 10 (PDCD10). [26]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Programmed cell death protein 10 (PDCD10). [27]
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⏷ Show the Full List of 9 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Programmed cell death protein 10 (PDCD10). [21]
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References

1 Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet. 2005 Jan;76(1):42-51. doi: 10.1086/426952. Epub 2004 Nov 12.
2 MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer.Prostate. 2016 May;76(6):543-51. doi: 10.1002/pros.23143. Epub 2016 Jan 15.
3 Loss of programmed cell death 10 activates tumor cells and leads to temozolomide-resistance in glioblastoma.J Neurooncol. 2019 Jan;141(1):31-41. doi: 10.1007/s11060-018-03017-7. Epub 2018 Nov 3.
4 Dual function of programmed cell death 10 (PDCD10) in drug resistance.Biomed Pharmacother. 2018 May;101:129-136. doi: 10.1016/j.biopha.2018.02.020. Epub 2018 Feb 23.
5 miRNA?6a?p and miR?6b?p inhibit the proliferation of bladder cancer cells by regulating PDCD10.Oncol Rep. 2018 Dec;40(6):3523-3532. doi: 10.3892/or.2018.6734. Epub 2018 Sep 26.
6 c-Myc regulates the coordinated transcription of brain disease-related PDCD10-SERPINI1 bidirectional gene pair.Mol Cell Neurosci. 2009 Sep;42(1):23-32. doi: 10.1016/j.mcn.2009.05.001. Epub 2009 May 13.
7 TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10.PLoS Biol. 2018 Nov 8;16(11):e3000051. doi: 10.1371/journal.pbio.3000051. eCollection 2018 Nov.
8 CDC42 Deletion Elicits Cerebral Vascular Malformations via Increased MEKK3-Dependent KLF4 Expression.Circ Res. 2019 Apr 12;124(8):1240-1252. doi: 10.1161/CIRCRESAHA.118.314300.
9 A novel large deletion in CCM1 gene in a Tunisian family.Rev Neurol (Paris). 2019 Mar;175(3):194-197. doi: 10.1016/j.neurol.2018.04.013. Epub 2018 Oct 9.
10 Novel exosomal miR-46146 transfer oxaliplatin chemoresistance in colorectal cancer.Clin Transl Oncol. 2020 Jul;22(7):1105-1116. doi: 10.1007/s12094-019-02237-1. Epub 2019 Nov 14.
11 miR-103 Functions as a Tumor Suppressor by Directly Targeting Programmed Cell Death 10 in NSCLC.Oncol Res. 2018 May 7;26(4):519-528. doi: 10.3727/096504017X15000757094686. Epub 2017 Jul 21.
12 Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis.APMIS. 2010 Oct;118(10):719-28. doi: 10.1111/j.1600-0463.2010.02669.x. Epub 2010 Aug 19.
13 Hereditary Multiple Cerebral Cavernous Malformations Associated with Wilson Disease and Multiple Lipomatosis.World Neurosurg. 2017 Sep;105:1034.e1-1034.e6. doi: 10.1016/j.wneu.2017.06.002. Epub 2017 Jun 8.
14 Familial Cerebral Cavernous Malformations. 2003 Feb 24 [updated 2023 Jul 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
15 First case of neutropenia and thrombocytopenia in the setting of cerebral cavernous malformation 3.Int J Hematol. 2019 Jul;110(1):95-101. doi: 10.1007/s12185-019-02626-w. Epub 2019 Mar 23.
16 CCM2-CCM3 interaction stabilizes their protein expression and permits endothelial network formation.J Cell Biol. 2015 Mar 30;208(7):987-1001. doi: 10.1083/jcb.201407129.
17 Effects of programmed cell death protein 10 on the Schistosoma japonicum female reproductive system.Acta Trop. 2020 Feb;202:105253. doi: 10.1016/j.actatropica.2019.105253. Epub 2019 Oct 31.
18 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
19 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
20 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.
21 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.
22 Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
23 Epigallocatechin-3-gallate (EGCG) protects against chromate-induced toxicity in vitro. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):166-75.
24 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.
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 Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
27 Molecular signatures of cytotoxic effects in human embryonic kidney 293?cells treated with single and mixture of ochratoxin A and citrinin. Food Chem Toxicol. 2019 Jan;123:374-384. doi: 10.1016/j.fct.2018.11.015. Epub 2018 Nov 11.