ToRNeDO
First-in-Class Approach to Targeted Protein Degradation
We configured ToRFLEx to address the challenging task of empirically discovering functional molecular glue degraders that enable Targeted Protein Degradation with our ToRNeDO strategy
Our system is the only one that can screen compounds in a cellular context, with a functional Ubiquitin Proteasome System (UPS), to identify hits if a pre-specified E3 ubiquitin ligase can actively lead to the degradation of the specific target of interest. Our system is capable of accessing >400 E3s. By selecting which biologically relevant E3s to include via our plug and play approach, we can simultaneously multiplex dozens of E3s for any given target.
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ToRNeDO discovers novel molecular glue degraders
We engineer cells to survive only when target protein is efficiently degraded via the cell’s UPS. Our empirical selection approach removes serendipity and introduces a deliberate and proprietary discovery technology to find molecular glues from a first pass screen.
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Compounds that recruit an E3 ubiquitin ligase to a neosubstrate
Molecular glues can act through various mechanisms – directly binding to an E3 ligase, stabilizing an existing interaction, or destabilizing a target protein by acting as an intramolecular glue. ToRNeDO is unbiased, and can discover molecular glue degraders that work by any of these mechanisms.
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To achieve productive protein degradation
Only productive ternary complexes that lead to polyubiquitination of the target protein leads to proteasomal degradation and hit detection. Any molecular glues indentified that directly bind to an E3 can also be used as ‘handles’ and form the basis of PROTACs to diversify their reach to additional protein targets.
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Target & E3 Precision
We select which target protein we seek to degrade and which E3s are best suited for the task, choosing these based on their expression patterns to ensure an optimal clinical benefit.
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Access Majority of E3s
By genetically encoding our E3 ligase specificity subunits, we are not limited to those with known ligands, biochemical purification protocols, or available structures. We can currently access >400 E3s and can choose multiple E3s to screen simultaneously by multiplexing in HTS format.
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First-pass Degradation
ToRNeDo can screen for compounds that can functionally degrade selected target proteins from the first pass, in a cellular context with a functional UPS. No need for lengthy downstream mechanistic deconvolution to identify what targets and E3s are involved.
Explore how our ToRPPIDO platform works to disrupt protein-protein interactions
ToRPPIDO
ToRPPIDO discovers compounds that can functionally disrupt a Protein-Protein Interaction
