G Protein-Coupled Receptors (GPCRs) represent the largest class of membrane proteins in humans and bind almost all of the known neurotransmitters and hormones that are released synaptically or secreted into the circulatory system. GPCRs are expressed in all tissue types and organs and are associated with many diseases.
The GPCR super-family includes around 400 medically relevant targets. To date more than 110 receptors have been exploited as drug targets, while most of the remaining are orphan (130) or under-characterized.
Ion channels are complex, pore-forming membrane proteins that modulate the flow of ions across the cell membrane and control, among other functions, the resting membrane potential and all electrical signaling of the cell.
The ion channel super-family includes around 280 medically relevant targets, including many important CNS targets. Of these, less than 20% have been exploited as drug targets. Traditional drug discovery approaches for ion channel-targeting drugs, such as high throughput screening, are not possible due to challenges related to expression of wild type proteins.
GPCRs, ion channels, and other membrane proteins are difficult to work with due to their hydrophobicity and flexible nature. Increasing stability/melting temperature has been shown to lead to increased homogeneity, better crystallizability, improved antigenicity and immunogenicity.
Abilita Bio has developed an approach, which allows for fast and efficient identification of mutation sets that impart substantial improvements over wild type membrane proteins. Our readout method is orders of magnitude faster than existing technologies, and allows for screening of multiple mutations at once (mutation sets), which can also uncover cooperative mutations. Additionally, our technology is applicable to Orphan Receptors, since we are able to create stabilized membrane proteins in apo form (unbound).
Our primary screening allows for the identification of EMPs™ characterized by:
1) Sufficient Expression Levels
EMPs™ have greater than ten-fold higher expression levels than wild type proteins.
2) Proper Molecular Folding
Proper folding is an indication of stability, and a requirement for trafficking.
3) Translocation to the Plasma Membrane
Appropriate delivery of receptor to cell surface is critical for drug discovery.
Our secondary screening evaluates and ranks production levels in human cell lines, thermostability, ligand binding and receptor signaling as well as other criteria specified by our partners. Our goal and commitment is to deliver a panel of the best performing EMPs™ to our partners within a few months.
For more information, please see the application pages, or contact us.