Membrane proteins are the targets of more than 50% of all existing therapeutic agents on the market. Low success rate (less than 1%) of selected therapeutic hits in pre-clinical and clinical phases is mainly due to the challenges of working with membrane protein in vitro that are difficult to stabilize and lack precision for necessary environment and the conformational nature of the target.
G.CLIPS Biotech created the first technology that overcomes these challenges. Our G.Screen® proprietary technology combines in one platfom : expression, purification, stabilization and functional characterization of membrane proteins in their pathology-like environment.
Drug, antibody and vaccine discovery
Native and structural stabilization of membrane proteins
Conformational stabilization in micelles and lipid bilayers
Generation of Lead-Like Candidates
Tissue-like membrane proteins stabilized in the desired conformation(s)
Membrane protein activation and binding validation assay
G. MIXES® :
Stabilized target for drug antibody and vaccine discovery
Membrane proteins stabilization upon extraction from native membranes is one of the biggest challenges for their in vitro use in early stages of drug and antibody discovery.
G.Screen® platform has the solution. We design, select and optimize tailor-made mixes, G.mixes®, for structural and conformational stabilization of membrane proteins. We thus express, purify and stablize membrane proteins targets, allowing to :
Develop an in vitro primary test directly on the purified and stablized target
Develop stabilized Antigens for generation of antibodies by Immunzation
Gain insight for drug and antibody discovery and generate first hits / binders / vaccine candidates
Generate different stabilized conformational states for the same target
G.SELECT® ASSAY :
Conformational selective screening for hits validation and lead generation
The same drug/antibody hit/lead could trigger different responses according to the conformational state of the target. This could be very difficult to assess in cellulo.
G.Screen® platform allows the performance of conformational selective screenings using G.Select® assay.
G.Select® assay combines G.mixes® and activation assay (G.Validation® assay) and enables to explore conformational complexity of membrane proteins. We thus obtain the perfect match between a desired conformational state and its best drug/antibody candidate.
Pathology-like target stabilized in the desired environment for lead optimization
Lipid composition membranes differs from one tissue to another (liver vs cardiac vs ….) and from one cell state to another (inflammation state, proliferation state…). This influences membrane protein function and pharmacology.
G.Lipidomics®, is a proprietary database of the lipid composition of the membranes of more than 20 tissues and cell types, allowing the reconstitution of a membrane protein in an environment mimicking the target tissue/cells in the specific pathophysiology.
G.Screen® platform combines G.Lipidomics® database and G.Mixes® technology to generate purified target expressed in the desired conformational state and in a tissue like environment.
G.VALIDATION® ASSAY :
In vitro functional assay for target validation, target/ candidate interaction
Interaction between membrane protein target and a drug/antibody candidate is currently assessed using either indirect cell based assays or biophysical binding technologies. Cell based assays doesn’t allow on target validation and candidates profiling in one single assay without costly experiments. Binding technologies (SPR, BLI etc…) lack for important phamacological profiling of the drug (agonist/antagonist/ PAM, NAM etc…).
G.CLIPS developed a proprietary cell free fluorescence-based assay that evaluates the conformational change of the receptor upon activation/inactivation and thus the pharmacological profiling of reference and candidate ligands.
G.Validation® assay is used at each step of the process and gives valuable insights and information to select and validate the best candidates from hits to clinical candidates
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