Enveric Biosciences Reports EB-003 BRET Receptor Engagement Assay Data
Enveric Biosciences a biotechnology company advancing novel neuroplastogenic small-molecule therapeutics to address psychiatric and neurological disorders, today announced new mechanistic data demonstrating that its lead candidate, EB-003, activates both Gq- and β-arrestin–mediated signaling downstream of the 5-HT₂A receptor. Multiple independent, peer-reviewed studies have previously shown that selective activation of 5-HT₂A receptor, by either Gq-biased or β-arrestin–biased agonists, can independently produce antidepressant- and anxiolytic-like effects in preclinical models, suggesting that therapeutic benefit can arise from activation of either pathway.
The new data was generated using proprietary bioluminescence resonance energy transfer (BRET) assays. Enveric developed and validated in-house BRET assays to characterize EB-003’s intracellular signaling profile because commercial assays capable of reliably measuring pathway-specific 5-HT₂A signaling were not available. The data demonstrate biologically relevant engagement of both Gq and β-arrestin pathways.
Enveric’s new data also indicate that EB-003 exhibits a modest preference toward β-arrestin over Gq signaling relative to serotonin, the native ligand of the receptor. Ongoing research is exploring the mechanistic significance of this apparent bias. Importantly, both pathways appear to be engaged at levels consistent with biological relevance.
Independent Academic Findings Support Pathway Separation
A recently published study in Nature employing BRET assays and complementary techniques provides additional mechanistic clarity regarding signaling downstream of 5-HT₂A.1 The study reports that Gi signaling downstream of 5-HT₂A was required for hallucinogenic effects in the experimental models evaluated, while Gq signaling mediated antidepressant- and anxiolytic-like benefits in preclinical systems. These findings indicate that therapeutic benefit and hallucinations may arise from distinct intracellular pathways.
“Growing mechanistic clarity around 5-HT₂A signaling strengthens confidence in the scientific foundation of our platform,” said Joseph Tucker, Ph.D., CEO of Enveric Biosciences. “Our proprietary BRET assay data show that EB-003 engages signaling pathways that prior peer-reviewed studies have linked to antidepressant- and anxiolytic-like effects in preclinical models.”
Dr. Tucker continued: “Independent academic research further suggests that hallucinogenic effects may arise from a distinct Gi-mediated mechanism. Those findings are consistent with our strategy of designing non-hallucinogenic neuroplastogens intended to deliver therapeutic benefit without the safety, monitoring, and scalability constraints associated with psychedelic compounds. Enveric is planning additional BRET testing of EB-003, including of the Gi pathway, to further characterize its unique signaling mechanisms.”
EB-003 is being developed to be a non-hallucinogenic neuroplastogen intended to support streamlined treatment paradigms, including potential at-home administration. The Company continues to advance EB-003 through IND-enabling studies.
About Enveric Biosciences
Enveric Biosciences is a biotechnology company focused on developing next-generation, small-molecule neuroplastogenic therapeutics that address unmet needs in psychiatric and neurological disorders. By leveraging a differentiated drug discovery platform and a growing library of patent protected chemical structures, Enveric is advancing a pipeline of novel compounds designed to promote neuroplasticity without hallucinogenic effects. Enveric’s lead candidate, EB-003, is the first known compound designed to selectively engage both 5-HT₂A and 5-HT₁B receptors with the potential to deliver fast-acting, durable antidepressant and anxiolytic effects with outpatient convenience.
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