Computational approaches to the prediction of blood-brain barrier permeability: A comparative analysis of central nervous system drugs versus secretase inhibitors for Alzheimer's disease.
This review summarizes progress made in the development of fully computational approaches to the prediction of blood-brain barrier (BBB) permeability of small molecules, with a focus on rapid computational methods suitable for the analysis of large compound sets and virtual screening. A comparative analysis using the recently developed Advanced Chemistry Development (ACD/Labs) Inc BBB permeability algorithm for the calculation of logBB values for known Alzheimer's disease medicines, selected central nervous system drugs and new secretase inhibitors for Alzheimer's disease, is presented. The trends in logBB values and the associated physiochemical properties of these agents as they relate to the potential for BBB permeability are also discussed.
Rishton
Gilbert M
GM
Channel Islands Alzheimer's Institute, California State University Channel Islands, One University Drive, Camarillo, CA 93012, USA. gilbert.rishton@csuci.edu
LaBonte
Kristen
K
Williams
Antony J
AJ
Kassam
Karim
K
Kolovanov
Eduard
E
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002199:Capillary Permeability; D002491:Central Nervous System Agents / Q000378:metabolism*; D003198:Computer Simulation; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D011480:Protease Inhibitors / Q000378:metabolism*
D002491:Central Nervous System Agents; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human