GlaxoSmithKline published studies on the activity of their drug Dabrafenib and the three mayor metabolites . Interestingly, measured half-lives for CDB and DDB were longer than for DB and HDB . The study of Ellens et al. reports that, based on in vitro antiproliferative IC50 measures, HDB and DDB should be potent inhibitors of BRAF-V600E, slightly less active than DB whereas the activity of CDB is largely reduced. Comparison of the affinity measures with the affinity ranking using MM-PBSA suggests that high values of the dielectric constant ( > 8) are appropriate to obtain the equivalent ranking of DB -HDB/DDB -CDB, from best to worst (compare Figure ).