Therapeutic Approach

Oncoceutics is developing a novel class of safe and effective cancer therapies called imipridones. Imipridones have a unique three-ring core structure and selectively target G protein-coupled receptors (GPCRs), the largest class of membrane receptors and a common target of approved drugs that are underexploited in oncology.  Despite being historically uncommon as targets in oncology, GPCRs control an array of critical prosurvival and stress signaling pathways that are often dysregulated in human cancer to favor cancer cell survival and propagation.

The ability of imipridones to target GPCRs with a high degree of selectivity represents a novel opportunity in oncology that generates remarkably safe and effective therapeutics. ONC201, the founding member of this novel class of therapies, is an orally active, safe, and selective antagonist of the GPCR Dopamine Receptor D-2 (DRD2). Antagonism of DRD2 has been shown to cause downstream activation of the integrated stress response and inactivation of Ras signaling, both of which have been proven clinically effective in oncology and have resulted in approved therapeutics such as bortexomib and cetuximab. ONC201 represents the first clinical opportunity to engage these proven signaling pathways by selectively targeting DRD2, which is overexpressed or otherwise dysregulated in many types of cancer.

The diagram above shows how ONC201 engages a differentiated network of critical signaling pathways that cancer cells rely on and to which they are particularly susceptible.

At a event hosted by Oncoceutics, Dr. Silvio Gutkind of UC San Diego, Dr. Keith Flaherty of Massachusetts General Hospital, and Dr. Joshua Allen of Oncoceutics spoke about the interaction between ONC201 and the DRD2, and the downstream pathways that interaction controls.