Classification of Drugs by CNS Access: An Insight from Quantitative Blood-Brain Transport Characteristics
Poster Apr 04, 2012
Kiril Lanevskij, Pranas Japertas and Remigijus Didziapetris, Advanced Chemistry Development Inc.
The ultimate goal of QSAR analysis focusing on blood-brain barrier penetration is the ability to discriminate between CNS active and inactive molecules. The objective of the current study was to establish the relationship between quantitative blood-brain transport parameters and qualitative data indicating whether the compound penetrates into the brain efficiently enough to exhibit action in the central nervous system (CNS).
Two quantitative characteristics were considered: brain/plasma equilibration rate (log [PS • fu,br]), and the extent of brain/plasma partitioning at equilibrium (log BB). Analysis of a diverse data set consisting of >1500 compounds from the World Drug Index (WDI) database with experimentally assigned brain penetration categories revealed that a linear combination of the above mentioned parameters allowed classification of drugs by CNS access with 94% accuracy. Furthermore, the devised classification score correlated well with the unbound brain/plasma partitioning coefficient (log Kp,uu), which is recognized as an unambiguous determinant of brain exposure. The obtained results confirm the validity of the proposed classification approach.
CiPA Phase 2 Study: validation of an automated microelectrode array (MEA) assay of hiPSC-derived cardiomyocyte electrophysiology for cardiac safety evaluationPoster
These results support the use of hSC-CM and MEA technology for preclinical assessment of proarrhythmic risk within the proposed CiPA paradigm, and, more generally, demonstrate that automation of the CM-MEA assay can achieve high reliability and throughput for cardiac risk assessment in vitro.READ MORE
A luminescent solar concentrator-based photomicroreactor for energy efficient continuous-flow photocatalysisPoster
The Luminescent Solar ConcentratorPhotomicroreactor
(LSC-PM) is an innovative device
for solar-powered continuous-flow photochemistry.