https://clincancerres.aacrjournals.org/content/clincanres/15/10/3617.full.pdflooks like it works in vitro but has some issues with effective dose levels and tolerability of those dose level... has certainly has an effect in vitro maybe hard to get to the site through oral dose and crossing the BBB with enough efficacy for GBM?
Conclusions: Higher and more frequent dosing of enzastaurin resulted in improved drug exposure but with unacceptable toxicity at the doses tested. Phosphorylated glycogen synthase 3 β may be a useful biomarker of the biological activity of enzastaurin. Enzas- taurin has activity in a subset of malignant glioma patients and warrants continued study in combination with other agents using a maximal once daily dose of 500 mg.
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... the median progression-free survival for the entire study group was only 1.4 months, and the median overall survival was 5.7 months.
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Patients in our study experienced unacceptable toxicity at all dose levels tested, in contrast to prior studies where enzastaurin was very well-tolerated. Toxicity seemed to be dose dependent because DLTs were largely observed with twice daily dosing, which was in turn associated with 50% to 90% higher drug ex- posures than was the daily dosing. Furthermore, in contrast to the prior phase I/II study, where increasing doses of enzastaurin from 500 to 900 mg/day did not result in increasing serum le- vels of the drug (14), our study did result in significant in- creases in total analyte exposure between the 500 and 800 mg once daily cohorts.
