Development of an Aryloxazole Derivative as a Brain-Permeable Anti-Glioblastoma Agent.

ABSTRACT: Glioblastoma drug development has been difficult due to the extremely low blood brain barrier (BBB) penetration of conventional anti-cancer agents. P-glycoprotein, an efflux membrane transporter, is responsible for the poor brain uptake of small and hydrophobic drug substances. To develop brain-penetrable anti-tumor agents, we designed colchicine derivatives containing an aryloxazole moiety, which is known to inhibit P-glycoprotein. Among those tested, an aryloxazole derivative named KIST-G1 showed the strongest anti-glioblastoma cell proliferation activity (IC₅₀ = 3.2 ± 0.8 nM). Compared to colchicine, KIST-G1 showed dramatically increased BBB-permeable properties presenting 51.7 ± 0.5 (10^-6 cm/s) parallel artificial membrane permeability assay (PAMPA) permeability a

SUBMITTER: Shin S 

PROVIDER: S-EPMC6835410 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature