Philadelphia, PA (July 1, 2019) – Oncoceutics, Inc. announced a scientific publication in the journal Leukemiademonstrating selective and potent agonism of the G-protein coupled receptor (GPCR) GPR132 by ONC212, an imipridone derivative of ONC201.
GPR132 is an orphan GPCR previously shown to play a tumor suppressor role in acute leukemias that has not been targeted therapeutically. The article shows that ONC212 binds to and activates GPR132 at nanomolar concentrations. GPR132 expression and activation of the integrated stress response was associated with ONC212 anti-cancer effects in acute myeloid leukemia preclinical models. The preclinical efficacy was observed as a single agent and synergistic in combination with the Bcl-2 inhibitor ABT-199.
These findings are consistent with a previous publicationon ONC212 safety and efficacy in preclinical models of pancreatic cancer, which also exhibits elevated GPR132 expression. ONC212 is protected by a composition of matter patent and its future Phase I/II clinical trials in refractory AML is the subject of an alliance between MD Anderson and Oncoceutics.
“Whereas our clinical programs that are ongoing with ONC201 or will commence shortly with ONC206 focus on specific antagonistic effects on Dopamine Receptor D2, the referenced publication clearly indicates the translational potential of ONC212 as the first GPR132 agonist for oncology that is poised for clinical introduction,” said Wolfgang Oster, MD, PhD, and Chief Executive Officer of Oncoceutics. “ONC212 adds another GPCR to our target list that have not been druggable so far and allows us to incorporate GPR132 as a predictive biomarker in the development program.”
“ONC212 belongs to the group of orphan GPCRs that have been extremely challenging targets for drug development despite their frequent dysregulation in malignant diseases,” said J. Silvio Gutkind, PhD, Associate Director of Basic Science at University of California, San Diego. “ONC212 is one of the first drug candidates discovered and developed by Oncoceutics to address this opportunity and it extends the utility of the imipridone platform into hematologic malignancies, as elegantly described in this manuscript.”
Oncoceutics, Inc. is a clinical-stage drug discovery and development company with a novel class of compounds, called “imipridones,” that selectively target G protein-coupled receptors for oncology. The lead compound to emerge from this program is ONC201, an orally active small molecule DRD2 antagonist. The company is supported by grants from the NCI, FDA, The Musella Foundation, and a series of private and public partnerships. Visit Oncoceuticsor contact Press@oncoceutics.comfor more information.