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BioAssay: AID 92023

Inhibition constant (Ki) for human intestinal peptide carrier

The utilization of the carrier protein PEPT1 for the absorption of peptidomimetic drug molecules is a promising strategy for oral drug administration and increasing bioavailability. In the absence of structural information on the binding mode of substrates to PEPT1, a computational study was conducted to explore the structural requirements for substrates and to derive a predictive model that may more ..
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 Tested Compounds
 Tested Compounds
All(104)
 
 
Active(3)
 
 
Unspecified(101)
 
 
 Tested Substances
 Tested Substances
All(104)
 
 
Active(3)
 
 
Unspecified(101)
 
 
AID: 92023
Data Source: ChEMBL (89213)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-24
Modify Date: 2013-11-15

Data Table ( Complete ):           Active    All
BioActive Compounds: 3
Description:
Title: Three-dimensional quantitative structure-activity relationship analyses of peptide substrates of the mammalian H+/peptide cotransporter PEPT1.

Abstract: The utilization of the carrier protein PEPT1 for the absorption of peptidomimetic drug molecules is a promising strategy for oral drug administration and increasing bioavailability. In the absence of structural information on the binding mode of substrates to PEPT1, a computational study was conducted to explore the structural requirements for substrates and to derive a predictive model that may be used for the design of novel orally active drugs. A comparative molecular field analysis (CoMFA) and a comparative molecular similarity indices analysis (CoMSIA) were performed on a series of 79 dipeptide-type substrates for which affinity data had been collected in a single test system under the same conditions. These studies produced models with conventional r(2) and cross-validated coefficient (q(2)) values of 0.901 and 0.642 for CoMFA and 0.913 and 0.776 for CoMSIA. The models were validated by an external test set of 19 dipeptides and dipeptide derivatives. CoMSIA contour maps were used to identify the recognition elements that are relevant for the binding of PEPT1 substrates. The 3D QSAR models provide an insight in the interactions between substrates and PEPT1 on the molecular level and allow the prediction of affinity constants of new compounds.
(PMID: 14667225)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Putative Target:

ChEMBL Target ID: 10561
Target Type: SINGLE PROTEIN
Pref Name: Oligopeptide transporter small intestine isoform
Synonyms: Intestinal H(+)/peptide cotransporter;Oligopeptide transporter; small intestine isoform;Peptide transporter 1;Solute carrier family 15 member 1;
Gene Name: PEPT1;SLC15A1;
Protein Accession: P46059;
Protein GI: 1172435;
Organism: Homo sapiens
Tax ID: 9606
Target Classification: transporter electrochemical h-symporter peptide dipeptide
Confidence: Homologous single protein target assigned
Relationship Type: Homologous protein target assigned
Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6Ki activity commentKi activity commentString
7Ki standard flagKi standard flagInteger
8Ki qualifierKi qualifierString
9Ki published valueKi published valueFloatmM
10Ki standard valueKi standard valueFloatnM
11Ki data validityKi data validityString

* Activity Concentration.

Data Table (Concise)
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