Think Bioscience’s Post

Think Bioscience is a synthetic biology company developing small molecule therapeutics against difficult-to-drug proteins. Founded in 2019 out of Boulder, Colorado, the company develops microbial systems to evolve targeted and readily synthesizable drug leads. Encoding a molecular objective into a microbial host to identify, build, and evolve small molecules. Despite advances in computational chemistry and structural biology, drug design remains exceedingly difficult. Approximately 90% of proteins in the human proteome remain 'undruggable' (i.e. they lack an obvious pocket for a drug to bind), and over 50% contain disordered regions that preclude detailed crystallographic analysis. As a result of these challenges, many entire classes of important proteins lack targeted therapeutics of any kind. Many compound libraries include molecules chosen for their synthetic accessibility, drug-like attributes (i.e. Lipinski's rule of five), or historical origin. As a result, many molecular trajectories remain unexplored simply because they’re different. On top of this, protein motion can reveal hidden sites that allow small molecules to control protein function from nonintuitive positions (i.e. a site distal to the active site of an enzyme). These sites, which are promising starting points for drug development, are challenging to find with existing biophysical methods. To solve this problems, Think uses biosynthetic machinery to explore a novel molecular search space in drug discovery. And discover small-molecule modulators of proteins that lack crystal structures, sample multiple conformations, or contain highly disordered regions. With microbial systems that can generate large quantities of promising molecules through simple fermentation. Think is focused on drugging protein tyrosine phosphatases (PTPs). That catalyze the hydrolytic dephosphorylation of tyrosine residues and contribute to a diseases from diabetes and cancer to autoimmunity, neurological disorders, deafness, and heart disease). Currently, there are no FDA-approved therapeutics that target PTPs. Think is also building a pipeline pursuing protein tyrosine kinases (PTKs), transcription factors, and targets with disordered regions.