Target Information
Target General Information | Top | |||||
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Target ID |
T95899
(Former ID: TTDC00142)
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Target Name |
Clusterin messenger RNA (Clusterin mRNA)
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Synonyms |
Testosteronerepressed prostate message 2 (mRNA); Testosterone-repressed prostate message 2 (mRNA); TRPM-2 (mRNA); NA1/NA2 (mRNA); Ku70binding protein 1 (mRNA); Ku70-binding protein 1 (mRNA); KUB1 (mRNA); Complementassociated protein SP40,40 (mRNA); Complement-associated protein SP-40,40 (mRNA); Complement cytolysis inhibitor (mRNA); Clusterin alpha chain (mRNA); Clusterin (mRNA); CLI (mRNA); Apolipoprotein J (mRNA); ApoJ (mRNA); Apo-J (mRNA); Agingassociated gene 4 protein (mRNA); Aging-associated gene 4 protein (mRNA); AAG4 (mRNA)
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Gene Name |
CLU
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Breast cancer [ICD-11: 2C60-2C6Y] | |||||
2 | Lung cancer [ICD-11: 2C25] | |||||
3 | Prostate cancer [ICD-11: 2C82] | |||||
Function |
Prevents stress-induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. Secreted isoform 1 protects cells against apoptosis and against cytolysis by complement. Intracellular isoforms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity. Nuclear isoforms promote apoptosis. Mitochondrial isoforms suppress BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Plays a role in the regulation of cell proliferation. Isoform 1 functions as extracellular chaperone that prevents aggregation of nonnative proteins.
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BioChemical Class |
mRNA target
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UniProt ID | ||||||
Sequence |
MMKTLLLFVGLLLTWESGQVLGDQTVSDNELQEMSNQGSKYVNKEIQNAVNGVKQIKTLI
EKTNEERKTLLSNLEEAKKKKEDALNETRESETKLKELPGVCNETMMALWEECKPCLKQT CMKFYARVCRSGSGLVGRQLEEFLNQSSPFYFWMNGDRIDSLLENDRQQTHMLDVMQDHF SRASSIIDELFQDRFFTREPQDTYHYLPFSLPHRRPHFFFPKSRIVRSLMPFSPYEPLNF HAMFQPFLEMIHEAQQAMDIHFHSPAFQHPPTEFIREGDDDRTVCREIRHNSTGCLRMKD QCDKCREILSVDCSTNNPSQAKLRRELDESLQVAERLTRKYNELLKSYQWKMLNTSSLLE QLNEQFNWVSRLANLTQGEDQYYLRVTTVASHTSDSDVPSGVTEVVVKLFDSDPITVTVP VEVSRKNPKFMETVAEKALQEYRKKHREE Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | Custirsen | Drug Info | Phase 3 | Lung cancer | [2] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | TCR Signaling Pathway | |||||
2 | FSH Signaling Pathway | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | CCKR signaling map ST | |||||
PID Pathway | [+] 1 PID Pathways | + | ||||
1 | Validated targets of C-MYC transcriptional repression | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Platelet degranulation | |||||
WikiPathways | [+] 1 WikiPathways | + | ||||
1 | Complement and Coagulation Cascades |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Over-expression of clusterin is a resistance factor to the anti-cancer effect of histone deacetylase inhibitors. Eur J Cancer. 2009 Jul;45(10):1846-54. | |||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800016680) | |||||
REF 3 | Phase II trial of OGX-011 in combination with docetaxel in metastatic breast cancer. Clin Cancer Res. 2009 Jan 15;15(2):708-13. | |||||
REF 4 | Custirsen (OGX-011): a second-generation antisense inhibitor of clusterin for the treatment of cancer. Expert Opin Investig Drugs. 2008 Dec;17(12):1955-62. |
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