ArticleJournal of medicinal chemistry2009
Molecular dynamics study of non-nucleoside reverse transcriptase inhibitor 4-[[4-[[4-[(E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (TMC278/rilpivirine) aggregates: correlation between amphiphilic properties of the drug and oral bioavailability.
Article in Journal of medicinal chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 17 citations in OpenAlex.
- Probing the free-state solution behavior of drugs and their tendencies to self-aggregate into nano-entities.Nature protocols · 2021Review
- Article
- Enzyme-instructed self-assembly: a multistep process for potential cancer therapy.Bioconjugate chemistry · 2015Review
- Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge.Journal of computer-aided molecular design · 2014Article
- Role of Ligand Reorganization and Conformational Restraints on the Binding Free Energies of DAPY Non-Nucleoside Inhibitors to HIV Reverse Transcriptase.Computational molecular bioscience · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278/rilpivirine is an anti-AIDS therapeutic agent with high oral bioavailability despite its high hydrophobicity. Previous studies established a correlation between ability of the drug molecule to form stable, homogeneous populations of spherical nanoparticles (approximately 100-120 nm in diameter) at low pH in surfactant-independent fashion and good oral bioavailability. Here, we hypothesize that the drug is able to assume surfactant-like properties under physiologically relevant conditions, thus facilitating formation of nanostructures in the absence of other surfactants. The results of all-atom molecular dynamics simulations indeed show that protonated drug molecules behave as surfactants at the water/aggregate interface while neutral drug molecules assist aggregate packing via conformational variability. Our simulation results suggest that amphiphilic behavior at low pH and intrinsic flexibility influence drug aggregation and are believed to play critical roles in the favorable oral bioavailability of hydrophobic drugs.
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Registered trials
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