ArticleMolecular pharmaceutics2010
Structural determinants for transport across the intestinal bile acid transporter using C-24 bile acid conjugates.
Article in Molecular pharmaceutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Novel nitroxide-bile acid conjugates inform substrate requirements for human bile acid transporters.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2023Article
- Synthesis and Evaluation of Bile Acid-Ribavirin Conjugates as Prodrugs to Target the Liver.Journal of pharmaceutical sciences · 2015Article
- Mechanistic interpretation of conventional Michaelis-Menten parameters in a transporter system.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2014Article
- In vivo effects of the pure aryl hydrocarbon receptor antagonist GNF-351 after oral administration are limited to the gastrointestinal tract.British journal of pharmacology · 2014Article
- An updated review on drug-induced cholestasis: mechanisms and investigation of physicochemical properties and pharmacokinetic parameters.Journal of pharmaceutical sciences · 2013Review
- Design and characterization of a novel fluorinated magnetic resonance imaging agent for functional analysis of bile Acid transporter activity.Pharmaceutical research · 2013Article
- Automation of the CHARMM General Force Field (CGenFF) I: bond perception and atom typing.Journal of chemical information and modeling · 2012Article
- Computational modeling to accelerate the identification of substrates and inhibitors for transporters that affect drug disposition.Clinical pharmacology and therapeutics · 2012Article
- Deconstructing 14-phenylpropyloxymetopon: minimal requirements for binding to mu opioid receptors.Bioorganic & medicinal chemistry · 2012Article
- Intrinsic energy landscapes of amino acid side-chains.Journal of chemical information and modeling · 2012Article
- Structural requirements of bile acid transporters: C-3 and C-7 modifications of steroidal hydroxyl groups.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2012Article
- Computational ligand-based rational design: Role of conformational sampling and force fields in model development.MedChemComm · 2011Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The human apical sodium dependent bile acid transporter (hASBT) reabsorbs gram quantities of bile acid daily and is a potential prodrug target to increase oral drug absorption. In the absence of a high resolution hASBT crystal structure, 3D-QSAR modeling may prove beneficial in designing prodrug targets to hASBT. The objective was to derive a conformationally sampled pharmacophore 3D-QSAR (CSP-SAR) model for the uptake of bile acid conjugates by hASBT. A series of bile acid conjugates of glutamyl chenodeoxycholate were evaluated in terms of K(m) and normalized V(max) (normV(max)) using hASBT-MDCK cells. All monoanionic conjugates were potent substrates. Dianions, cations and zwitterions, which bound with a high affinity, were not substrates. CSP-SAR models were derived using structural and physicochemical descriptors, and evaluated via cross validation. The best CSP-SAR model for K(m) included two structural and two physiochemical descriptors, where substrate hydrophobicity enhanced affinity. A best CSP-SAR model for K(m)/normV(max) employed one structural and three physicochemical descriptors, also indicating hydrophobicity enhanced efficiency. Overall, the bile acid C-24 region accommodated a range of substituted anilines, provided a single negative charge was present near C-24. In comparing uptake findings to prior inhibition results, increased hydrophobicity enhanced activity, with dianions and zwitterions hindering activity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.