Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore

We present in vivo pharmacokinetic studies of the top analogues with evidence of brain penetration. We also report a targeted siRNA-based screen which suggests a possible role for mTOR and Akt in DNA repair inhibition by this class of drugs. Taken together, these data reveal a new class of mibefradil-based DNA repair inhibitors which can be further advanced into pre-clinical testing and eventually clinical trials, as potential GBM radiosensitizers.PMID:33953843 | PMC:PMC8092340 | DOI:10.18632/oncotarget.27933

Source: Oncotarget - May 6, 2021 Category: Cancer & Oncology Authors: Sateja Paradkar James Herrington Adam Hendricson Piyasena Hewawasam Mark Plummer Denton Hoyer Ranjini K Sundaram Yulia V Surovtseva Ranjit S Bindra Source Type: research