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Many fundamental cell functions such as muscle contraction and nerve transmission rely on the electrical signals produced by the movement of positively and negatively charged ions across the cell membrane. One competent method to record current flowing across the whole cell or single ion channel is the patch-clamp technique.
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A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules
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Recent advances in high throughput screening for ADME properties.

Timothy J Carlson1, Michael B Fisher

  • 1Amgen Inc, 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.

Combinatorial Chemistry & High Throughput Screening
|March 14, 2008
PubMed
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Drug metabolism and pharmacokinetic (DMPK) screening is crucial for drug discovery. Recent advances in in vitro, in vivo, and in silico methods enhance early decision-making for drug candidates.

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Area of Science:

  • Pharmacology
  • Drug Discovery
  • Biochemistry

Background:

  • Drug discovery programs synthesize numerous molecules, requiring extensive data for candidate selection.
  • Drug metabolism and pharmacokinetic (DMPK) data are essential for identifying viable drug candidates.
  • Established in vitro and in vivo DMPK screens are routinely used in drug discovery.

Purpose of the Study:

  • To review recent advances in experimental and computational methods for generating DMPK information.
  • To summarize new approaches in metabolic clearance, CYP inhibition, in vivo exposure, and distribution studies.
  • To highlight improvements in bioanalytical techniques for drug discovery.

Main Methods:

  • Review of published literature on recent advancements in DMPK assays.
  • Focus on experimental techniques for metabolic clearance, CYP inhibition, and in vivo studies.
  • Inclusion of in silico (computational) methods for predicting ADME properties.
  • Discussion of optimized bioanalytical approaches for method development, sample preparation, and analyte detection.

Main Results:

  • Significant progress has been made in experimental assays for metabolic clearance and CYP inhibition.
  • New methods have improved the assessment of in vivo exposure and drug distribution.
  • In silico models for absorption, distribution, metabolism, and excretion (ADME) properties have advanced.
  • Bioanalytical techniques show improvements in sensitivity and efficiency.

Conclusions:

  • Recent advancements in DMPK methodologies are improving the quality and speed of data generation.
  • Enhanced DMPK information enables earlier and more informed decision-making in drug discovery.
  • Continued innovation in both experimental and computational approaches will further accelerate drug development.