Oncotarget: A New Class of Radiosensitizers for Glioblastoma

Apr 29, 2021

Researchers at Yale University created a new class of radiosensitizers for glioblastoma based on mibefradil, with improved potency and reduced off-target effects. They synthesized and tested 140 analogs, selecting top 12 for further in vivo studies. These analogs were shown to cross the blood-brain barrier and accumulate in mouse brain tissue, offering potential for enhanced radio sensitization in treating glioblastoma.

Ask episode

Chapters

Transcript

Episode notes

Innovative Radio Sensitizers for Glioblastoma

00:00 • 2min

Development and Evaluation of Promising Myphradil Analogs for Glioblastomas

02:20 • 3min

In the cover paper of this week's issue of Oncotarget (Volume 12, Issue 9), titled, "Creation of a new class of radiosensitizers for glioblastoma based on the mibefradil pharmacophore," researchers conducted a study to create mibefradil analogs as superior radiosensitizers for glioblastomas. In the current study, based on their previous findings, the researchers from Yale University used structure activity relationship analysis and EJ-DR assays to create, synthesize, and profile a series of 140 mibefradil analogs. Their goal was to develop superior mibefradil analogues, with reduced off-target effects and improved potency. After successfully reducing the known off-target liabilities of mibefradil, the team selected the top 12 analogues for further in vitro and in vivo pharmacokinetic studies. These analogs were tested in vivo to verify that they cross the blood-brain barrier and accumulate in mouse brain tissue. “We then tested the pharmacokinetic parameters of the synthesized analogues and validated their ability to cross the blood-brain barrier (BBB) and accumulate in mouse brain tissue, at levels similar to that observed with mibefradil.” DOI - https://doi.org/10.18632/oncotarget.27933 Full text - https://www.oncotarget.com/article/27933/text/ Correspondence to - Yulia V. Surovtseva - yulia.surovtseva@yale.edu and Ranjit S. Bindra - ranjit.bindra@yale.edu Keywords - glioblastoma, radiosensitizers, mibefradil, DNA repair, alternative non-homologous end joining About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957