pgp - publications
Atom-based enumeration: New eribulin analogues with low susceptibility to P-glycoprotein-mediated drug efflux.
Bioorg Med Chem Lett. 2012 Oct 22;
Authors: Yu MJ, Zheng W, Tendyke K
A series of eribulin analogues was evolved in silico through iterative atom-based enumeration employing a genetic algorithm-derived survival function to minimize predicted PgP-mediated drug efflux. Representatives of the virtual series were subsequently synthesized in the laboratory and tested in vitro for PgP-susceptibility. These new computer-inspired derivatives were found to exhibit high cell growth inhibitory activity and to be among the least sensitive to P-glycoprotein-mediated drug efflux in the eribulin series, thereby validating this approach to in silico molecular design.
PMID: 23141916 [PubMed - as supplied by publisher]