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BioAssay: AID 360150

Inhibition of mouse Oat1-mediated [3H]PAH uptake in Xenopus oocytes after 1 hr

Organic anion transporters (OATs, SLC22) interact with a remarkably diverse array of endogenous and exogenous organic anions. However, little is known about the structural features that determine their substrate selectivity. We examined the substrate binding preferences and transport function of olfactory organic anion transporter, Oat6, in comparison with the more broadly expressed transporter, more ..
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 Tested Compounds
 Tested Compounds
All(45)
 
 
Active(12)
 
 
Unspecified(33)
 
 
 Tested Substances
 Tested Substances
All(45)
 
 
Active(12)
 
 
Unspecified(33)
 
 
AID: 360150
Data Source: ChEMBL (508179)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-26
Modify Date: 2014-05-24

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Solute carrier family 22 member 6; AltName: Full=Kidney-specific transport protein; AltName: Full=Novel kidney transcript; Short=mNKT; AltName: Full=Organic anion transporter 1; AltName: Full=Renal organic anion transporter 1; Short=mROAT1
Description ..   
Protein Family: MFS
Comment ..   

Gene:SLC22A6          More BioActivity Data..
BioActive Compounds: 12
Description:
Title: Structural variation governs substrate specificity for organic anion transporter (OAT) homologs. Potential remote sensing by OAT family members.

Abstract: Organic anion transporters (OATs, SLC22) interact with a remarkably diverse array of endogenous and exogenous organic anions. However, little is known about the structural features that determine their substrate selectivity. We examined the substrate binding preferences and transport function of olfactory organic anion transporter, Oat6, in comparison with the more broadly expressed transporter, Oat1 (first identified as NKT). In analyzing interactions of both transporters with over 40 structurally diverse organic anions, we find a correlation between organic anion potency (pKi) and hydrophobicity (logP) suggesting a hydrophobicity-driven association with transporter-binding sites, which appears particularly prominent for Oat6. On the other hand, organic anion binding selectivity between Oat6 and Oat1 is influenced by the anion mass and net charge. Smaller mono-anions manifest greater potency for Oat6 and di-anions for Oat1. Comparative molecular field analysis confirms these mechanistic insights and provides a model for predicting new OAT substrates. By comparative molecular field analysis, both hydrophobic and charged interactions contribute to Oat1 binding, although it is predominantly the former that contributes to Oat6 binding. Together, the data suggest that, although the three-dimensional structures of these two transporters may be very similar, the binding pockets exhibit crucial differences. Furthermore, for six radiolabeled substrates, we assessed transport efficacy (Vmax) for Oat6 and Oat1. Binding potency and transport efficacy had little correlation, suggesting that different molecular interactions are involved in substrate binding to the transporter and translocation across the membrane. Substrate specificity for a particular transporter may enable design of drugs for targeting to specific tissues (e.g. olfactory mucosa). We also discuss how these data suggest a possible mechanism for remote sensing between OATs in different tissue compartments (e.g. kidney, olfactory mucosa) via organic anions.
(PMID: 17553798)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: cell-based format

Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface 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 valueFloat
10Ki standard valueKi standard valueFloatnM
11Ki data validityKi data validityString
12Ki binding domainsKi binding domainsString
13Ki activity commentKi activity commentString
14Ki standard flagKi standard flagInteger
15Ki qualifierKi qualifierString
16Ki published valueKi published valueFloatμM
17Ki standard valueKi standard valueFloatnM
18Ki data validityKi data validityString
19Ki binding domainsKi binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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