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Macrocycles offer the potential to combine the most desirable properties of biologic medicines including potency and selectivity as well as qualities of small molecule medicines such as cell permeability, oral dosing and ease of manufacturing.
We are working to create treatments to effectively combat untreatable cancers and other severe illnesses, enhancing the lives of patients and their loved ones.
Bridging the Gap
Most drugs today fall into one of two categories: small molecules or biologics. Each type has positive characteristics as well as inherent limitations. Macrocycles occupy a middle ground between the two, giving them the potential to combine the preferred attributes of each while overcoming some of their shortcomings, making macrocycles the best choice for certain therapeutic targets.
Macrocycles derived from nature have been used therapeutically for several decades, and more recently macrocycles have been recognized as a potential solution to address therapeutic targets that are considered otherwise undruggable. This has brought a renewed focus on understanding how to make fully synthetic macrocycles with improved properties, including passive cell permeability and oral bioavailability, and we have built the MXMOTM platform to address these goals.
Circle Pharma’s founders, Matt Jacobson and Scott Lokey, studied the properties of synthetic macrocycles and developed new tools for understanding and predicting their cell permeability. Extending their work, Circle Pharma’s scientists have demonstrated their ability to accurately and systematically design macrocycles that can penetrate the cell membrane and potently and selectively bind to challenging targets like cyclins.
With Circle Pharma’s advanced technology, the MXMOTM platform, our team has been able to better understand and predict how varying types of macrocycles may be able to penetrate cells, be orally bioavailable, exhibit desirable drug-like qualities, and be manufactured at large scale.
The MXMOTM platform was designed to combine computationally driven, structure-based design along with advanced, fully synthetic macrocycle chemistry. Through this platform, our scientists screen vast permeability-biased virtual and physical chemical libraries to identify early hit compounds. Artificial Intelligence (AI), Machine Learning (ML), and rigorous physics-based simulations are used to assess multiple potential alternative designs and to rapidly explore structure-activity relationships for hit-to-lead progression. Diverse variations of these compounds are then synthesized in the lab, utilizing both natural and unnatural chemical building blocks, many of which are custom and proprietary to Circle Pharma, to optimize the lead investigational macrocycles.
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