Our science
What are Interdictors™?
Interdictors™ are orally bioavailable small molecule drugs that inhibit protein synthesis by the ribosome in a context-dependent manner. Interdictors™ are “linkerless” heterobifunctional molecules that bind a pocket of the peptidyl-transferase center (PTC) where one half of the molecule binds the ribosomal RNA and the other half has substituents that interact with the elongating nascent polypeptide as it emerges in the PTC. These complementary physiochemical interactions with the advancing nascent polypeptide chain slow the rate of protein synthesis, inhibiting target protein production.
Our focus
Focus on oncology and neurodegenerative diseases
Indications within oncology and neurodegeneration are among the many possible applications where Interdictors™ can uniquely exploit the qualities of highly validated yet elusive targets, including:
Intrinsically disordered proteins
Intrinsically disordered proteins (IDPs), including MYC, have historically been ‘undruggable’ due to their lack of a defined ‘pocket’ or binding site for small molecule drugs. Interdictors™ can uniquely address IDPs in addition to structured targets as all proteins transiently have a linear, ordered conformation inside the ribosome peptidyl-transferase center (PTC) where Interdictors™ inhibit their translation.
Rapid turnover proteins
Rapid turnover proteins, like MYC, have also long been considered difficult-to-address with traditional small molecules due to the fast kinetics required for inhibition and keeping up with new synthesis. While this may be a liability for traditional MOAs, this is a vulnerability that Interdictors™ uniquely exploit to robustly deplete the targets from the cell.
Accumulating/Aggregation-prone proteins
Many neurodegenerative diseases, including Alzheimer’s, derive from the accumulation and aggregation of proteins that lead to neuronal cell death. Recent work with antisense oligonucleotides has shown that reduction of protein production can improve symptoms and slow disease progression. Interdictors™ provide an oral, brain-penetrant small molecule approach to inhibit the synthesis of these aggregation-prone proteins.
Repeat-driven proteinopathies
Repeated sequence motifs such as the poly-CAG (poly-glutamine) associated with Huntington’s Disease or spinocerebellar ataxias (SCAs) are unique targets for the Interdictor™ modality. These repeated motifs in a single nascent polypeptide allow for cumulative inhibitory interactions with an Interdictor™, permitting selectivity for long poly-glutamine expansions found in pathogenic alleles compared to short poly-glutamine expansions in wild-type alleles.
OUR Platform
The Interdict Platform
Our discovery platform integrates rigorous computational science, structural biology, biophysics, biochemistry, medicinal chemistry, genomics, and cellular biology. These outputs fuel our proprietary discovery engine, called the INTERDICTionary™ at the interface of AI, bioinformatics, genomics, and structure-based drug design to drive the discovery of novel Interdictors™.
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See how Interdictors™ work
