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BioAssay: AID 630741

Inhibition of human PAT1-mediated L-[3H]proline uptake in human Caco2 cells after 10 mins by liquid scintillation counting

The proton-coupled amino acid transporter hPAT1 has recently gained much interest due to its ability to transport small drugs thereby allowing their oral administration. A three-dimensional quantitative structure-activity relationship (3D QSAR) study has been performed on its natural and synthetic substrates employing comparative molecular similarity indices analysis (CoMSIA) to investigate the more ..
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AID: 630741
Data Source: ChEMBL (788189)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-23

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Proton-coupled amino acid transporter 1; Short=Proton/amino acid transporter 1; Short=hPAT1; AltName: Full=Solute carrier family 36 member 1
Description ..   
Protein Family: Solute carrier families 5 and 6-like; solute binding domain
Comment ..   

Gene:SLC36A1          More BioActivity Data..
Tested Compounds:
Description:
Title: Three-dimensional quantitative structure-activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1).

Abstract: The proton-coupled amino acid transporter hPAT1 has recently gained much interest due to its ability to transport small drugs thereby allowing their oral administration. A three-dimensional quantitative structure-activity relationship (3D QSAR) study has been performed on its natural and synthetic substrates employing comparative molecular similarity indices analysis (CoMSIA) to investigate the structural requirements for substrates and to derive a predictive model that may be used for the design of new prodrugs. The cross-validated CoMSIA models have been derived from a training set of 40 compounds and the predictive ability of the resulting models has been evaluated against a test set of 10 compounds. Despite the relatively narrow range of binding affinities (K(i) values) reliable statistical models with good predictive power have been obtained. The best CoMSIA model in terms of a proper balance of all statistical terms and the overall contribution of individual properties has been obtained by considering steric, hydrophobic, hydrogen bond donor and acceptor descriptors (q(cv)(2)=0.683, r(2)=0.958 and r(PRED)(2)=0.666). The 3D QSAR model provides insight in the interactions between substrates and hPAT1 on the molecular level and allows the prediction of affinity constants of new compounds. A pharmacophore model has been generated from the training set by means of the MOE (molecular operating environment) program. This model has been used as a query for virtual screening to retrieve potential new substrates from the small-molecule, 'lead-like' databases of MOE. The affinities of the compounds were predicted and 11 compounds were identified as possible high-affinity substrates. Two selected compounds strongly inhibited the hPAT mediated l-[(3)H]proline uptake into Caco-2 cells constitutively expressing the transport protein.
(PMID: 21955456)
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
BAO: Assay Format: cell-based format
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
2Ki activity commentKi activity commentString
3Ki standard flagKi standard flagInteger
4Ki qualifierKi qualifierString
5Ki published valueKi published valueFloatmM
6Ki standard valueKi standard valueFloatnM
7Ki data validityKi data validityString
8pKi activity commentpKi activity commentString
9pKi standard flagpKi standard flagInteger
10pKi qualifierpKi qualifierString
11pKi published valuepKi published valueFloatmM
12pKi standard valuepKi standard valueFloatmM
13pKi data validitypKi data validityString

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View All Data
Classification
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