Our breakthrough systems biology platform combines pharmacology, biology and mathematics to accelerate the hit-to-lead process in GPCR drug discovery

How It Works

1. G Protein Coupled Receptors & Ligands

Our platform is applicable to all GPCR targets, indication or type of compound, e.g. biologics or small molecules, full/partial agonists, antagonists, orthosteric or allosteric ligands. We perform all our assays using unlabeled ligands, thereby excluding labeling artefacts.

We express your target GPCR in cell lines containing signaling biosensors. We use a small set of reference ligands to calibrate the signaling responses of your target GPCR.

Our platform is applicable to all GPCR targets, indication or type of compound, e.g. biologics or small molecules, full/partial agonists, antagonists, orthosteric or allosteric ligands. We perform all our assays using unlabeled ligands, thereby excluding labeling artefacts.

We express your target GPCR in cell lines containing signaling biosensors. We use a small set of reference ligands to calibrate the signaling responses of your target GPCR.

Assays

2. Time resolved cellular signaling assays

We perform time-resolved cellular signaling assays to obtain kinetic profiles of your test compounds. This approach captures cellular signaling cascades to a much higher extent than static end-point assays.

We perform time-resolved cellular signaling assays to obtain kinetic profiles of your test compounds. This approach captures cellular signaling cascades to a much higher extent than static end-point assays.

3. Proprietary systems biology models

We generate mathematical models using ordinary differential equations (ODEs) to describe the specific signaling pathways of your target GPCR. We then analyze the kinetic profiles of your test compounds using this unique systems biology model.

We generate mathematical models using ordinary differential equations (ODEs) to describe the specific signaling pathways of your target GPCR. We then analyze the kinetic profiles of your test compounds using this unique systems biology model.

Compounds to Clustered

4. Clustering compounds based on novel parameters

Our systems biology analysis provides you with a multitude of novel ligand parameters. We then cluster your test compounds based on this analysis. We can easily spot outliers (off-target effects) and help you to identify compounds with the most promising profiles for in vivo testing

Our systems biology analysis provides you with a multitude of novel ligand parameters. We then cluster your test compounds based on this analysis. We can easily spot outliers (off-target effects) and help you to identify compounds with the most promising profiles for in vivo testing

In Vivo

5. Better prediction of in vivo effects

We can therefore assist in correlating the new compound parameter profiles to in vivo data provided by you – thereby honing in on promising compounds in an early stage. This accelerates the hit-to-lead identification process.

The InterAx Edge

Full ligand range
No ligand labeling
Time-resolved assays

Full ligand range

No limitations on ligand types

No ligand labeling

Ensuring better predictions

Time-resolved assays

More accurately characterize in-cell
behaviour

The InterAx Edge

ligand-triad-20200120 1 (2)

Full ligand range

No limitations on ligand types

label-20200120 1 (1)

No ligand labeling

Ensuring better predictions

single-assay-20200120 1 (1)

Time-resolved assays

More accurately characterize in-cell
behaviour

Asthma Case Study

We exemplified the power of our platform by predicting asthma drug action using our proprietary beta2-adrenergic receptor ODE model.

Selected Supporting Literature

Systems Biology

The European Research Network on Signal Transduction (ERNEST): Toward a Multidimensional Holistic Understanding of G Protein-Coupled Receptor Signaling

Sommer ME, Selent J, Carlsson J, De Graaf C, Gloriam DE, Keseru GM, Kosloff M, Mordalski S, Rizk A, Rosenkilde MM, Sotelo E, Tiemann JKS, Tobin A, Vardjan N, Waldhoer M, Kolb P. (2020) ACS Pharmacol Transl Sci. 3:361-370.

G Protein-Coupled Receptor Signaling Networks from a Systems Perspective

Roth S, Kholodenko BN, Smit MJ, Bruggeman FJ (2015). Mol Pharmacol., 88: 604-16.

A conformation-equilibrium model captures ligand-ligand interactions and ligand-biased signalling by G-protein coupled receptors

Roth S, Bruggeman FJ (2014). FEBS J, 281: 4659-71.

Competing G protein-coupled receptor kinases balance G protein and β-arrestin signaling

Heitzler D, Durand G, Gallay N, Rizk A, Ahn S, Kim J, Violin JD, Dupuy L, Gauthier C, Piketty V, Crépieux P, Poupon A, Clément F, Fages F, Lefkowitz RJ,Reit er E. (2012). Mol Syst Biol. 8:590.

A general computational method for robustness analysis with applications to synthetic gene networks

Rizk A, Batt G, Fages F, Soliman S (2009). Bioinformatics, 25:i169-78

On the Analysis of Numerical Data Time Series in Temporal Logic

Fages F, Rizk A. (2007). Computational Methods in Systems Biology, CMSB’07 Edinburgh. Springer-Verlag LNBI, 4695 :48-63.

Novel Compounds

A Focus on Unusual ECL2 Interactions Yields β2 -Adrenergic Receptor Antagonists with Unprecedented Scaffolds

Scharf MM, Zimmermann M, Wilhelm F, Stroe R, Waldhoer M, Kolb P. (2020) ChemMedChem. 15:882-890.

Technology - Biosensors & Assays

New Insights into Arrestin Recruitment to GPCRs

Spillmann M, Thurner L, Romantini N, Zimmermann M, Meger B, Behe M, Waldhoer M, Schertler GFX, Berger P. (2020) Int J Mol Sci. 21:4949.

Systems NMR: single-sample quantification of RNA, proteins and metabolites for biomolecular network analysis

Yaroslav Nikolaev, Nina Ripin, Martin Soste, Paola Picotti, Dagmar Iber & Frédéric H.-T. Allain (2019) Nature Methods volume 16, pages743–749

Quantification of Molecular Interactions in Living Cells in Real Time using a Membrane Protein Nanopattern

Reichmuth AM, Zimmermann M, Wilhelm F, Frutiger A, Blickenstorfer Y, Fattinger C, Waldhoer M, Vörös J. (2020) Anal Chem. 92:8983-8991.

Real-time trafficking and signaling of the glucagon-like peptide-1 receptor

Roed SN, Wismann P, Underwood CR, Kulahin N, Iversen H, Cappelen KA, Schäffer L, Lehtonen J, Hecksher-Soerensen J, Secher A, Mathiesen JM, Bräuner-Osborne H, Whistler JL, Knudsen SM, Waldhoer M. (2014) Mol Cell Endocrinol. 382:938-49.

Segmentation and quantification of subcellular structures in fluorescence microscopy images using Squassh

Rizk A, Paul G, Incardona P, Bugarski M, Mansouri M, Niemann A, Ziegler U, Berger P, Sbalzarini IF (2014). Nat Protoc., 9:586-96.

Arrestin-1 engineering facilitates complex stabilization with native rhodopsin.

Haider RS, Wilhelm F, Rizk A, Mutt E, Deupi X, Peterhans C, Mühle J, Berger P, Schertler GFX, Standfuss J, Ostermaier MK (2019). Sci Rep, 9:439.

Molecular mechanism of phosphorylation-dependent arrestin activation

Ostermaier MK, Schertler GF, Standfuss J. (2014) Curr Opin Struct Biol. 29:143-51.

The project PICARD has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 880322

AI Integration

As one of the few winners of the EU Horizon 2020 funding, InterAx is integrating artificial intelligence into its proprietary systems biology platform. The EU project is called PICARD and is aimed at further accelerating lead identification and enabling de novo drug design.

We are open to a range of collaborations,
from pilot projects to long-term partnerships