ONC206

ONC206

ONC206 is a DRD2 antagonist and ClpP agonist with nanomolar potency that demonstrates enhanced non-competitive DRD2 antagonism relative to ONC201, and disruption of DRD2 homodimers. ONC206 exhibits a distinct gene expression profile as well as single agent and combinatorial efficacy with ONC201 in cells with acquired resistance to ONC201. ONC206 is effective in preclinical models of difficult-to-treat neuroendocrine tumors and high-grade gliomas. It affects some of the same downstream pathways as ONC201, including activation of the integrated stress response and inhibition of Ras signaling, leading to selective killing of tumor cells.

The first-in-human clinical trial for adults with recurrent primary central nervous system tumors is ongoing at the National Institute of Health (NCT04541082).   

References: 

  1. Varun Vijay Prabhu, Sara Morrow, Caroline A. Cuoco, Abed R. Kawakibi, Jinkyu Jung, Neel Madhukar, Matthew J. Garnett, Ultan McDermott, Cyril H. Benes, Robert Wechsler-Reya, Lakshmi Anantharaman, Neil Charter, Joseph B. Rucker, Benjamin J. Doranz, Joel Basken, Olivier Elemento, R. Benjamin Free, David R. Sibley, Martin Stogniew, Wolfgang Oster, Mark R. Gilbert, Sharon DeMorrow. IND-enabling characterization of ONC206 as the next bitopic antagonist for oncology [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5688.
  2. Varun Prabhu, Caroline Cuoco, Jinkyu Jung, Sara Morrow, Abed Rahman Kawakibi, Blair Willette, Marilyn Day, Lakshmi Anantharaman, Neil Charter, Joseph Rucker, Benjamin Doranz, Joel Basken, Martin Stogniew, Mark Gilbert, R Free, David Sibley, Joshua Allen, DDRE-33. MOLECULAR DIFFERENTIATION OF IMIPRIDONES ONC201 AND ONC206, Neuro-Oncology, Volume 22, Issue Supplement_2, November 2020, Page ii68, https://doi.org/10.1093/neuonc/noaa215.278