Leading the Way in Membrane Protein Research
leadXpro specializes in structure-based drug discovery for membrane proteins.
Achievements as of December 2022:
Total number of membrane protein targets established: 61 (23 ion channels, 22 GPCRs, 13 transporters, 3 enzymes).
Target structural system established, allowing for the visualisation of small molecules interactions: 25
Novel drug targets structurally enabled: 7
We have an integrated platform for membrane protein biochemistry, biophysics and structural biology, including X-ray crystallography and cryo-EM.
From Target Gene to Lead Integrated Drug Discovery
leadXpro core technology
Construct engineering
leadXpro has expertise in engineering a wide range of membrane protein targets. Tailored for specific downstream drug discovery applications, our platform integrates rational and AI-assisted design with unique high-throughput screening technologies.
leadXpro unique technology
iBax HT Construct Screening
leadXpro’s iBax platform addresses a key bottleneck in membrane protein structural biology: identifying mutations to increase target stability and expression. Combining rational, AI-assisted construct design with a unique method for high-throughput construct assessment in insect cells, hundreds of variants can be screened in just a few weeks, unlocking the protein target for in vitro characterisation.
leadXpro core technology
Protein Purification
High-quality protein samples are the key to producing high-resolution structures. leadXpro has developed sophisticated methods for membrane protein expression, solubilization and purification and is continuing to develop novel technologies and workflows to produce high yields of purified, functional membrane proteins.
leadXpro unique technology
Pro-Macrobody Binder Technology
Nanobodies are powerful tools for membrane protein structural biology. To enhance their function, leadXpro has developed and patented Pro-Macrobodies, which combine nanobodies with a selected fusion protein, via a precision-engineered rigidified linker. This is a transformative tool for structural analysis of small and flexible membrane proteins, providing a large and rigid feature to aid particle picking and alignment in cryo-EM analysis or to build crystal contacts for X-ray crystallography targets.
Read more about Pro-Macrobodies here
leadXpro core technology
X-ray Crystallography
leadXpro is a leader in the field of membrane protein X-ray crystallography for drug discovery and has established expertise in handling the toughest targets. Our strategic location in close proximity to the Swiss Light Source (SLS) and the SwissFEL provides privileged access not only to high-end facilities, but also to the latest technological developments.
leadXpro unique technology
SwissFEL and Serial Crystallography
leadXpro’s commitment to innovation focuses on pushing the boundaries of serial and time-resolved X-ray crystallography, to probe the structural dynamics of membrane proteins for drug discovery. leadXpro co-founder Dr. Rafael Abela lead the construction of the SwissFEL facility and its pioneering use of femtosecond electron laser (FEL) technology. FELs produce very short and brilliant X-ray pulses. Coupled with serial delivery methods, this opens up exciting possibilities to work with delicate membrane protein crystals and explore time-resolved protein dynamics upon ligand binding. leadXpro is working together with key experts in the field to develop new methods to enable these pioneering experiments.
leadXpro core technology
Swiss Light Source Beamline
leadXpro is an industrial partner of the PXII beamline for Macromolecular Crystallography. This allows us to set up and screen many high-throughput crystallisation experiments and provides preferential access to beamtime for data collection. leadXpro actively contributes to the development of PXII as a reliable, high-quality and high-throughput industrial beamline. Full confidentiality is ensured for commercial projects.
leadXpro core technology
Cryo-Electron Microscopy
leadXpro has a successful platform for Cryo-EM of membrane proteins. We have determined numerous high-resolution structures, greatly impacting drug discovery projects. To yield the best results for challenging proteins, we carefully optimize all parameters, from grid freezing and data collection to structure determination and interpretation.
Read about our structures of Kv3.1, LptDE, TRPV4 and Cryosparc
leadXpro core technology
State-of-the-art TEM in-house
leadXpro established cryo-EM grid freezing and EM screening capabilities in-house. High end Titan Krios 300 kV measurements are done at BioEM in Basel and DCI Lausanne.
leadXpro core technology
Biophysical analysis
leadXpro’s biophysical platform draws on numerous methods, including GCI, MST, CPM and nanoDSF to provide high-quality binding and kinetic information, crucial for hit-to-lead optimisation. We analyse ligand binding stoichiometry, show target engagement and perform competition assays to assess allosteric binding.
leadXpro core technology
GCI - WAVEdelta by Creoptix
leadXpro’s biophysical platform adopts innovative technologies, such as the WAVEsystem manufactured by Creoptix, which provides high quality binding and kinetic data.
Read more about the partnership here and about Creoptix here.
leadXpro core technology
nanoDSF & DLS – Prometheus Panta by Nanotemper
Nano Differential Scanning Fluorimetry (nanoDSF) and Dynamic Light Scattering (DLS) are utilized at leadXpro for obtaining a wide range of information on protein quality, target-ligand interactions or formulation screening. Read more about the technology here.
leadXpro core technology
In Silico Ligand Design
leadXpro’s computational chemistry platform excels in analysis of ligand interactions, refinement of models into experimental data, molecular dynamics simulations of protein conformational change and virtual screening of large IP-free ligand libraries for hit generation.
leadXpro unique technology
Patented Lead Compounds
leadXpro uses its unique platform for membrane protein science and structural analysis to advance its drug discovery program, with patented lead compounds in oncology and inflammation.
Read more about our work here.
leadXpro core technology
Construct engineering
leadXpro has expertise in engineering a wide range of membrane protein targets. Tailored for specific downstream drug discovery applications, our platform integrates rational and AI-assisted design with unique high-throughput screening technologies.
leadXpro unique technology
iBax HT-Construct Screening
leadXpro’s iBax platform addresses a key bottleneck in membrane protein structural biology: identifying mutations to increase target stability and expression. Combining rational, AI-assisted construct design with a unique method for high-throughput construct assessment in insect cells, hundreds of variants can be screened in just a few weeks, unlocking the protein target for in vitro characterisation.
leadXpro core technology
Protein Purification
High-quality protein samples are the key to producing high-resolution structures. leadXpro has developed sophisticated methods for membrane protein expression, solubilization and purification and is continuing to develop novel technologies and workflows to produce high yields of purified, functional membrane proteins.
leadXpro unique technology
Pro-Macrobody Binder Technology
Nanobodies are powerful tools for membrane protein structural biology. To enhance their function, leadXpro has developed and patented Pro-Macrobodies, which combine nanobodies with a selected fusion protein, via a precision-engineered rigidified linker. This is a transformative tool for structural analysis of small and flexible membrane proteins, providing a large and rigid feature to aid particle picking and alignment in cryo-EM analysis or to build crystal contacts for X-ray crystallography targets.
Read more about Pro-Macrobodies here
leadXpro core technology
X-ray Crystallography
leadXpro specialises in membrane protein X-ray crystallography for drug discovery. To date, X-ray crystallography has produced the most high-resolution data for drug discovery. We are pioneering techniques for serial and time-resolved X-ray crystallography, to probe the structural dynamics of drug binding. Find out more about our work here and here.
leadXpro unique technology
SwissFEL and Serial Crystallography
leadXpro’s commitment to innovation focuses on pushing the boundaries of serial and time-resolved X-ray crystallography, to probe the structural dynamics of membrane proteins for drug discovery. leadXpro co-founder Dr. Rafael Abela lead the construction of the SwissFEL facility and its pioneering use of femtosecond electron laser (FEL) technology. FELs produce very short and brilliant X-ray pulses. Coupled with serial delivery methods, this opens up exciting possibilities to work with delicate membrane protein crystals and explore time-resolved protein dynamics upon ligand binding. leadXpro is working together with key experts in the field to develop new methods to enable these pioneering experiments. Find out more about our work here and here.
leadXpro core technology
Swiss Light Source Beamline
leadXpro is an industrial partner of the PXII beamline for Macromolecular Crystallography. This allows us to set up and screen many high-throughput crystallisation experiments and provides preferential access to beamtime for data collection. leadXpro actively contributes to the development of PXII as a reliable, high-quality and high-throughput industrial beamline. Full confidentiality is ensured for commercial projects.
leadXpro core technology
Cryo-Electron Microscopy
leadXpro has a successful platform for Cryo-EM of membrane proteins. We have determined numerous high-resolution structures, greatly impacting drug discovery projects. To yield the best results for challenging proteins, we carefully optimize all parameters, from grid freezing and data collection, to structure determination and interpretation.
leadXpro core technology
State-of-the-art TEM in-house
leadXpro established cryo-EM grid freezing and EM screening capabilities inhouse. High end Titan Krios 300 kV measurements are done at BioEM in Basel and DCI Lausanne.
leadXpro core technology
Biophysical analysis
leadXpro’s biophysical platform draws on numerous methods, including GCI, MST, CPM and nanoDSF to provide high-quality binding and kinetic information, crucial for hit-to-lead optimisation. We analyse ligand binding stoichiometry, show target engagement and perform competition assays to assess allosteric binding.
leadXpro core technology
GCI - WAVEdelta by Creoptix
leadXpro’s biophysical platform adopts innovative technologies, such as the WAVEsystem manufactured by Creoptix, which provides high quality binding and kinetic data. Read about our structures of Kv3.1, LptDE, TRPV4 and Cryosparc
leadXpro core technology
nanoDSF & DLS – Prometheus Panta by Nanotemper
Nano Differential Scanning Fluorimetry (nanoDSF) and Dynamic Light Scattering (DLS) are utilized at leadXpro for obtaining a wide range of information on protein quality, target-ligand interactions or formulation screening. Read more about the technology here.
leadXpro core technology
In Silico Ligand Design
leadXpro’s computational chemistry platform excels in analysis of ligand interactions, refinement of models into experimental data, molecular dynamics simulations of protein conformational change and virtual screening of large IP-free ligand libraries for hit generation.
leadXpro unique technology
Patented Lead Compounds
leadXpro uses its unique platform for membrane protein science and structural analysis to advance its drug discovery program, with patented lead compounds in oncology and inflammation. Read more about our work here.
