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.
Novel lead optimization strategy of BACE I inhibitors for the treatment of Alzheimer’s disease by Quantitative Structure-Activity Relationship (QSAR) and Physiologically-Based Pharmacokinetics (PBPK) modelingPoster
In this study, we introduce an innovative in silico-based high throughput lead optimization strategy with QSAR and PBPK modelings using StarDrop™, ADMET predictor® and GastroPlus®.READ MORE
Platform Agnostic Data Processing Routine for Targeted and Untargeted Metabolite Identification in Drug DiscoveryPoster
A discussion of a new informatics solution that addresses common challenges in metabolite identification and characterization--from LC/MS data processing and metabolites prediction to reporting and databasing of assembled biotransformation knowledge.READ MORE
The Pathogen Box: A Catalyst for Neglected Disease Drug DiscoveryPoster
Modelled after the Malaria Box, the Pathogen Box contains ~400 diverse drug-like molecules active against neglected diseases of interest such as Chagas disease, cryptosporidiosis, hookworm, sleeping sickness, leishmaniasis, lymphatic filariasis, malaria, onchocerciasis, schistosomiasis, trichuriasis, tuberculosis.READ MORE
Comments | 0 ADD COMMENT
Pfizer, Scripps Partner on DNA-Encoded Library Tech
News Jan 11, 2017