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BioAssay: AID 347584

Induction of apoptosis in human U251 cells assessed as increase in full length caspase 8 level after 24 hrs by western blot

Multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid in cancer cell lines inhibited the proteasome and induced apoptosis and heme synthesis. The most potent prodrug was butyryloxymethyl 5-amino-4-oxopentanoate (1a). The metabolically released formaldehyde from the prodrugs was the dominant factor affecting cell viability by a ROS-dependent mechanism and was responsible for rapid more ..
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 Tested Compounds
 Tested Compounds
All(3)
 
 
Active(3)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Active(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 347584
Data Source: ChEMBL (495613)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2013-07-05

Data Table ( Complete ):           Active    All
BioActive Compounds: 3
Description:
Title: Novel multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid display improved anticancer activity independent and dependent on photoactivation.

Abstract: Multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid in cancer cell lines inhibited the proteasome and induced apoptosis and heme synthesis. The most potent prodrug was butyryloxymethyl 5-amino-4-oxopentanoate (1a). The metabolically released formaldehyde from the prodrugs was the dominant factor affecting cell viability by a ROS-dependent mechanism and was responsible for rapid phosphorylation of H2AX, suppression of the cell survival protein c-myc, and transient elevation in the expression of p21. 1a, which differs from 2a by releasing butyric instead of pivalic acid, was a more potent inducer of heme and acetylated H4 expression and induced apoptosis through activation of caspase 9. 1a and 1b specifically increased the level of the photosensitizer protoporphyrin 9, leading to enhancement of cell death by photodynamic therapy (PDT). The advantage of these multifunctional prodrugs over 5-ALA is their greater potency in the non-PDT mechanism of cancer cell killing and their ability to also augment PDT.
(PMID: 19007111)
Comment
Putative Target:

ChEMBL Target ID: 80559
Target Type: CELL-LINE
Cell Line: U251
Tissue: Brain glioma
Pref Name: U251
Organism: Homo sapiens
Tax ID: 9606
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
ChEMBL Assay Type: Functional

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Assay Cell Type: U251

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat

Data Table (Concise)
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