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BioAssay: AID 371991

Drug uptake in human Caco-2 cells assessed as intracellular 5-aminolaevulinic acid level per mg of protein at 1 mM after 4 hrs

Twenty-seven dipeptide derivatives of general structure Ac-Xaa-ALA-OR were synthesized as potential prodrugs for 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). Xaa is an alpha-amino acid, chosen to provide a prodrug with appropriately tailored lipophilicity and water solubility. Although no simple correlation is observed between downstream production of protoporphyrin IX (PpIX) in more ..
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 Tested Compounds
 Tested Compounds
All(5)
 
 
Unspecified(5)
 
 
 Tested Substances
 Tested Substances
All(5)
 
 
Unspecified(5)
 
 
 Related BioAssays
 Related BioAssays
AID: 371991
Data Source: ChEMBL (520020)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2013-07-06

Data Table ( Complete ):           All
Tested Compounds:
Description:
Title: Improved peptide prodrugs of 5-ALA for PDT: rationalization of cellular accumulation and protoporphyrin IX production by direct determination of cellular prodrug uptake and prodrug metabolization.

Abstract: Twenty-seven dipeptide derivatives of general structure Ac-Xaa-ALA-OR were synthesized as potential prodrugs for 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT). Xaa is an alpha-amino acid, chosen to provide a prodrug with appropriately tailored lipophilicity and water solubility. Although no simple correlation is observed between downstream production of protoporphyrin IX (PpIX) in PAM212 keratinocytes and HPLC-derived descriptors of compound lipophilicity, quantification of prodrug uptake reveals that most of the dipeptides are actually more efficiently accumulated than ALA in PAM212 and also A549 and Caco-2 cell lines. Subsequent ALA release is the limiting factor, which emphasizes the importance of decoupling prodrug uptake and intracellular metabolization when assessing the efficacy of ALA derivatives for PDT. In agreement with PpIX fluorescence studies, at a concentration of 0.1 mM, l-Phe derivatives 4m and 4o, and l-Leu, l-Met, and l-Glu derivatives 4f, 4k, and 4u, exhibit significantly enhanced photoxicity in PAM212 cells compared to ALA.
(PMID: 19492812)
Comment
Putative Target:

ChEMBL Target ID: 80054
Target Type: CELL-LINE
Cell Line: Caco-2
Tissue: Colon adenocarcinoma cells
Pref Name: Caco-2
Organism: Homo sapiens
Tax ID: 9606
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
ChEMBL Assay Type: ADMET

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Assay Cell Type: Caco-2

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Drug uptake activity commentDrug uptake activity commentString
2Drug uptake standard flagDrug uptake standard flagInteger
3Drug uptake qualifierDrug uptake qualifierString
4Drug uptake published valueDrug uptake published valueFloatug
5Drug uptake standard valueDrug uptake standard valueFloatug

Data Table (Concise)
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