Publication in Nature Chemistry demonstrates benefits of native mass spectrometry in interrogating target ecosystems and drug discovery

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Mass therapy

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Publication in Nature Chemistry demonstrates benefits of native mass spectrometry in interrogating target ecosystems and drug discovery

  • Joint publication in Nature Chemistry between scientists at OMass Therapeutics and the co-founding team of Professor Dame Carol Robinson at the University of Oxford

  • Data demonstrate the ability of native mass spectrometry (MS) to interrogate the pharmacology of the beta-1 adrenergic receptor (β1AR), a G protein-coupled receptor (GPCR)

  • The discovery of endogenous zinc ion as a positive allosteric modulator in a well-studied receptor illustrates the potential of native MS to uncover new insights that may be important for drug discovery

BeefFord, UUK – November 10 2022 – OMass Therapeutics (“OMass” or “the Company”), a biotechnology company that identifies drugs against highly validated target ecosystems, today highlights the potential benefits of native mass spectrometry (MS) in drug discovery through his new publication “Mass spectrometry captures biased signaling and allosteric modulation of β1 adrenergic receptor” published today in Nature Chemistry1.

In this publication, the authors demonstrate how native MS can be used to study the pharmacology of GPCRs using β1AR as a model system. Being able to combine the sensitivity and near-atomic mass resolution of the mass spectrometer, while preserving receptor-G protein interactions, allowed the authors to monitor, with high sensitivity, the full spectrum of receptor pharmacology. in vitro. Due to mass differences between different G proteins, the authors were also able to distinguish whether a ligand is able to promote signaling biased towards a specific pathway.

The authors also discovered an endogenous zinc molecule associated with the receptor. This cation has been shown to be a positive allosteric modulator of β1AR and demonstrates the potential of native MS to discover new insights that may be important for drug discovery. For example, regulating zinc binding or mimicking its mechanism with a small molecule may provide a novel pathway to modulate β1AR kinetics or signaling for therapeutic purposes.

These examples highlight two key benefits of using native MS in drug discovery, namely: reconnecting the two fundamental drivers of pharmacology, binding and function; and querying a native ecosystem with high precision.

Professor Dame Carol Robinson, Co-Founder of OMass Therapeutics and Chair of the Scientific Advisory Board, said: “Our results demonstrate that native MS can be used to reconnect the two fundamental drivers of pharmacology, binding and function. From a practical point of view, GPCRs have represented a major challenge for native MS. Overcoming these challenges allowed us to monitor attenuated G-protein coupling driven by a wide range of ligands, underscoring the sensitivity and robustness of our approach.

I am also delighted that despite the fact that β1AR is a well-studied receptor, we were able to find a previously unknown endogenous zinc molecule associated with the receptor, which could have implications for the design of novel allosteric modulators.

Originally spun off from the University of Oxford, OMass commercialized Professor Dame Carol Robinson’s research on native MS to develop its proprietary drug discovery platform, OdyssION™. The platform integrates new biochemical techniques, next-generation native mass spectrometry and personalized chemistry, to enable the interrogation of protein interactions in its native ecosystem while avoiding the bewildering complexity of the cell.

This latest publication demonstrates some of the key advantages offered by OMass’ OdyssION™ platform in the search for new drugs against undermedicated or previously intractable targets. OMass is advancing a pipeline of small molecule therapeutics in rare diseases and immunological conditions that target GPCRs, solute carriers and complex-bound proteins.

Co-author Ali Jazayeri PhD, scientific director of OMass added: “GPCRs represent one of the most important protein target classes for drug discovery, with more than 30% of clinically marketed drugs active against this family of receptors. But, despite their prevalence as therapeutic targets, challenges remain in the drug treatment of these receptors.

We believe that our native MS platform, as this latest publication demonstrates, opens new possibilities for developing drugs against novel GPCR targets, as well as other target classes such as solute carriers and complex-bound proteins. .

  1. https://www.nature.com/articles/s41557-022-01041-9

Legend: Interrogating Protein Complexes with Native Mass Spectrometry
Copyright: Oxford University

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About OMass Therapeutics

OMass Therapeutics is a biotechnology company that discovers drugs against highly validated target ecosystems, such as membrane proteins or intracellular complexes. The company’s unique OdyssION™ technology platform includes new biochemistry techniques, next-generation native mass spectrometry and personalized chemistry. This allows OMass to interrogate not only the target, but also the target’s interaction with its native ecosystem, regardless of the bewildering complexity of the cell. The result is cell system fidelity with cell-free precision. OMass is advancing a pipeline of small molecule therapeutics in rare diseases and immunological conditions, which target solute carriers, complex-bound proteins and GPCRs.

Based in Oxford, UK, OMass has raised over $150m (£119m) from a leading international syndicate of investors including Syncona, Oxford Science Enterprises, GV, Northpond Ventures and Sanofi Ventures.

To learn more, visit www.omass.com. Follow us on LinkedIn and Twitter.

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