Publication in Nature Communications Confirms DRD2 as Target of ONC201

Philadelphia, PA (Nov. 19, 2019) – Oncoceutics, Inc. announced a publication in the journal Nature Communications demonstrating selective antagonism of the G-protein coupled receptor (GPCR) dopamine receptor D2 (DRD2) by Oncoceutics’ lead candidate imipridone, ONC201.

ONC201 was found to specifically bind and antagonize DRD2, and its functionally redundant family member DRD3, without affecting other dopamine receptors, other GPCRs, nuclear hormone receptors, kinases, or other drug targets of FDA-approved cancer therapies. Additionally, a biologically inactive isomer of ONC201 did not antagonize DRD2, indicating that antagonism of this receptor may be linked to anti-cancer efficacy as shown in other publications (Clinical Cancer Research and Neoplasia).

The publication also describes the novel approach taken by Oncoceutics collaborators in the laboratory of Olivier Elemento, PhD, Director of the Englander Institute for Precision Medicine at Weill Cornell Medicine. The researchers used a novel machine-learning platform, called BANDIT, created in the Elemento Lab that suggested DRD2 as a target of ONC201. This method used the molecular structure of ONC201, its in vitro efficacy profile, and its publicly available bioactivity assay results as inputs to compare ONC201 against all small molecules with known targets.
 
“This publication represents years of collaborative work that uncovered DRD2 as the first known binding target of ONC201,” said Joshua Allen, PhD and Senior Vice President of R&D of Oncoceutics. “Along with downstream biomarkers, the dopamine pathway has guided tumor type selection and interpretation of activity of ONC201 in clinical trials. So far, we have observed the most robust single agent efficacy in malignancies that exhibit dysregulation of the dopamine pathway and grow in a dopamine-rich microenvironment, such as midline gliomas.”

“Our findings have helped uncover imipridone small molecules as a unique chemical scaffold for targeting GPCRs,” said Dr. Elemento. “We are pleased to see the clinical translation of our precision medicine efforts in ONC201 clinical trials and hope this information can be used to identify additional indications for this new therapy.”
 
“The unique mechanism of action of ONC201 is now well defined,” said Martin Stogniew, PhD and Chief Development Officer of Oncoceutics.  “The most conserved downstream effect of ONC201 in tumor cells is activation of the integrated stress response. Several additional downstream effects, such as dual inactivation of Akt/ERK, induction of TRAIL and DR5, and degradation of Myc also occur in many tumor models, along with immunostimulatory effects involving NK cells and cancer stem cell depletion. These effects aggregately explain the broad antitumor activity observed in multiple models and are likely trigged by the interaction ONC201 with DRD2 and/or ClpP, a recently uncovered additional binding target of the molecule.”
 
For further reference, please refer to additional publications on ONC201 and imipridone small molecules. 
 
About Oncoceutics
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 first 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 Oncoceutics for more information

Publication in Nature Communications Confirms DRD2 as Target of ONC201

Publication in Nature Communications Confirms DRD2 as Target of ONC201

alexvarney

2 weeks
5 Views
Share
Want to watch this again later?
Sign in to add this video to a playlist. Login
0 0
Category:
Up Next Autoplay
Caris Life Sciences and Ambry Genetics Partner to Advance Cancer Care
Caris Life Sciences and Ambry Genetics Partner to Advance Cancer Care
Category: News
2 Views
Cancer-News 1 day
Long-Term Results from Phase 3 ALTA-1L Trial
Long-Term Results from Phase 3 ALTA-1L Trial
Category: Non-Small Cell Lung Cancer
26 Views
Cancer-News 2 days
Mount Sinai Receives $1 Million Grant for Prostate Cancer Research
Mount Sinai Receives $1 Million Grant for Prostate Cancer Research
Category: News
2 Views
Cancer-News 2 days
Treatment-Free Survival, With and Without Toxicity
Treatment-Free Survival, With and Without Toxicity
Category: Kidney Cancer
10 Views
kidneycancer 2 days
Phase 2 Study of Lenvatinib Plus Pembrolizumab for Disease Progression After PD-1/PD-L1
Phase 2 Study of Lenvatinib Plus Pembrolizumab for Disease Progression After PD-1/PD-L1
Category: Kidney Cancer
1 Views
kidneycancer 2 days
What's To Come in Modern Imaging Technology
What's To Come in Modern Imaging Technology
Category: Kidney Cancer
4 Views
kidneycancer 3 days
Moleculin Announces Additional Positive Interim Results from Phase 1/2 Clinical Studies of Annamycin in Acute Myeloid Leukemia
Moleculin Announces Additional Positive Interim Results from Phase 1/2 Clinical Studies of Annamycin in Acute Myeloid Leukemia
Category: Acute Myelogenous Leukemia
5 Views
Cancer-News 3 days
CytoDyn Reports Early Results from First Patient in its Phase 1b/2 CCR5+ Metastatic Triple-Negative Breast Cancer Trial
CytoDyn Reports Early Results from First Patient in its Phase 1b/2 CCR5+ Metastatic Triple-Negative Breast Cancer Trial
Category: Breast Cancer
6 Views
Cancer-News 3 days
Modern Imaging Technology
Modern Imaging Technology
Category: Kidney Cancer
10 Views
kidneycancer 3 days
ASH Releases New Clinical Practice Guidelines on Immune Thrombocytopenia
ASH Releases New Clinical Practice Guidelines on Immune Thrombocytopenia
Category: News
3 Views
Cancer-News 4 days