As targeted protein degradation (TPD) gains increasing momentum in drug discovery. ComInnex is also developing its expertise in this field. Our aim is to provide a toolkit of products and services that enables discovery research in both the pharmaceutical and agro/crop science oriented targeted protein degradation and in particular the design and synthesis of proteolysis-targeted chimeras (commonly known as protacs) or their components. We call this the Protein Degradation Chimera Toolkit. The toolkit has the following components.
Intelligent Compound design and selection
The ComInnex Fast Compound Design and Validation Platform (FCDVP) is a workflow, method and software platform for rapidly deriving new compounds that are validated with in silico models and checked for novelty and uniqueness. We apply FCDVP to the design of all our E3 ligase ligands and linkers in the Protein Degradation Chimera Toolkit, it can also be applied to the search for new POI (Protein of Interest) ligands too.
In our own internal validation projects we have generated a set of novel oncology targeted lead compounds under patenting, IAP and Cereblon E3 ligase binder sets and over 1,000 linkers for TPD. In addition FCDVP has been used to select a set of novel compounds that have demonstrated efficacy in COVID-19 related screens.
E3 Ligase ligands
We currently offer two sets of E3 ligase ligands for IAP and for Cereblon. The binding efficacy of the compounds has been confirmed via in silico models. The compounds in our libraries are available for purchase and integration into your TPD programmes. Whilst we continue to work on further E3 ligases we can also apply FCDVP to any E3 ligase suggested or requested by our customers.
Our ever increasing linker library contains both rigid and semi-flexible linkers. All compounds have been checked for novelty.
Linker Conjugated Ligase Binders
Combining elements from our sets of E3 ligase ligands and the linker library we can propose vast virtual libraries of protein degrader building blocks being partial chimeras.
The virtual libraries can be validated in silico and for synthetic feasibility.
As a further stage ComInnex can synthesize the selected compounds from the generated virtual library.
Linker conjugated POI libraries
Our wide selection of diverse building blocks and linkers allow us to prepare various libraries containing linker conjugates for HT screening to find novel POI ligands. The new approach may speed up the development of novel protein degraders from the POI side. The reverse approach of the identified POI-linker conjugates may help in finding the best ligases for protein degradation and characterized as a ComInnex Reverse Protein Targeted Chimera (REPROTAC) approach.
We have extensive experience on the synthesis of both partial and full protacs.
Projects can be undertaken on fixed fee or an FTE basis depending on the complexity and size of the project.
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