Artificial Membrane Technologies to Assess Transfer and Permeation of Drugs in Drug Discovery

Immobilized Artificial Membrane (IAM) chromatography columns have been used to model the in vivo distribution of drug discovery compounds. Regis Technologies Inc., the manufacturer, had to replace the silica support and consequently introduced a new IAM.PC.DD2 column that shows slightly different selectivity towards acidic and basic compounds. The application of the new IAM.PC.DD2 columns has been evaluated and the in vivo distribution models have been compared with the previous batches of columns. It was found that due to the improved endcapping of the silica, some of the positively charged drug molecules showed shorter retention than previously published. Therefore, the column system suitability data have been updated. However, these differences do not significantly affect the previously published models for the volume of distribution, brain tissue binding and drug efficiency. Therefore, the published models can be used with the new IAM.PC.DD2 columns.

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Advances in immobilized artificial membrane (IAM) chromatography for novel drug discovery

Expert Opinion on Drug Discovery ◽

10.1517/17460441.2016.1160886 ◽

2016 ◽

Vol 11 (5) ◽

pp. 473-488 ◽

Cited By ~ 25

Author(s):

Fotios Tsopelas ◽

Theodosia Vallianatou ◽

Anna Tsantili-Kakoulidou

Keyword(s):

Drug Discovery ◽

Artificial Membrane ◽

Immobilized Artificial Membrane ◽

Novel Drug

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How can we better realize the potential of immobilized artificial membrane chromatography in drug discovery and development?

Expert Opinion on Drug Discovery ◽

10.1080/17460441.2020.1718101 ◽

2020 ◽

Vol 15 (3) ◽

pp. 273-276 ◽

Cited By ~ 2

Author(s):

Anna Tsantili-Kakoulidou

Keyword(s):

Drug Discovery ◽

Artificial Membrane ◽

Drug Discovery And Development ◽

Membrane Chromatography ◽

Immobilized Artificial Membrane ◽

Immobilized Artificial Membrane Chromatography

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Validating ADME QSAR Models Using Marketed Drugs

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/24725552211017520 ◽

2021 ◽

pp. 247255522110175

Author(s):

Vishal Siramshetty ◽

Jordan Williams ◽

Ðắc-Trung Nguyễn ◽

Jorge Neyra ◽

Noel Southall ◽

...

Keyword(s):

Drug Discovery ◽

Chemical Structure ◽

Scientific Literature ◽

Aqueous Solubility ◽

Quantitative Structure Activity Relationship ◽

Artificial Membrane ◽

Structure Activity ◽

Qsar Models ◽

Permeability Assay ◽

Tier I

Problems with drug ADME are responsible for many clinical failures. By understanding the ADME properties of marketed drugs and modeling how chemical structure contributes to these inherent properties, we can help new projects reduce their risk profiles. Kinetic aqueous solubility, the parallel artificial membrane permeability assay (PAMPA), and rat liver microsomal stability constitute the Tier I ADME assays at the National Center for Advancing Translational Sciences (NCATS). Using recent data generated from in-house lead optimization Tier I studies, we update quantitative structure–activity relationship (QSAR) models for these three endpoints and validate in silico performance against a set of marketed drugs (balanced accuracies range between 71% and 85%). Improved models and experimental datasets are of direct relevance to drug discovery projects and, together with the prediction services that have been made publicly available at the ADME@NCATS web portal ( https://opendata.ncats.nih.gov/adme/ ), provide important tools for the drug discovery community. The results are discussed in light of our previously reported ADME models and state-of-the-art models from scientific literature. Graphical Abstract [Figure: see text]

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