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High throughput artificial membrane permeability assay for blood-brain barrier
Li Di1, Edward H Kerns, Kristi Fan
1Discovery Analytical Chemistry, Chemical Sciences, Wyeth Research, 08543-8000, Princeton, NJ, USA. dil@wyeth.com
European Journal of Medicinal Chemistry
|April 2, 2003
Summary
A new assay predicts blood-brain barrier (BBB) penetration potential for drug candidates. This high-throughput, low-cost method aids early compound selection in CNS drug discovery.
Area of Science:
- Pharmacology
- Drug Discovery
- Medicinal Chemistry
Background:
- High-throughput screening and combinatorial chemistry have increased the number of potential drug candidates.
- Early assessment of blood-brain barrier (BBB) penetration is crucial for selecting central nervous system (CNS) drug candidates.
- Existing methods for BBB penetration prediction can be time-consuming or costly.
Purpose of the Study:
- To introduce a modified parallel artificial membrane permeation assay (PAMPA) for predicting blood-brain barrier penetration (PAMPA-BBB).
- To provide a rapid, cost-effective, and reproducible method for assessing BBB permeability early in drug discovery.
Main Methods:
- Development of the PAMPA-BBB assay using 30 diverse commercial drugs.
- Validation of the PAMPA-BBB assay with 14 compounds from Wyeth Research.
- Utilizing artificial membrane technology to mimic the biological BBB.
Main Results:
- The PAMPA-BBB assay demonstrated high success in predicting passive BBB penetration.
- The assay is suitable for high-throughput screening, offering low cost and reproducibility.
- Successful validation with both commercial and research compounds.
Conclusions:
- The PAMPA-BBB assay is a valuable tool for predicting passive blood-brain barrier penetration.
- This assay accelerates drug discovery by enabling efficient compound selection and guiding synthesis for CNS properties.
- The PAMPA-BBB assay offers a practical and reliable method for early-stage drug development.