Traditional design of small molecule therapies has focused on specific, disease-associated protein targets which have led to the development of many breakthrough medicines. However, once a drug enters the body, it interacts with dozens, if not hundreds, of proteins before it is eliminated from the body. These off-target interactions can impact the safety of a drug or may lead to drug repurposing opportunities. Cyclica's drug-centric, proteome-wide approach focuses on a drug's polypharmacology — all the proteins it interacts with — to provide insights into repurposing efforts, target identification, lead prioritization, and adverse effect elucidation.
Cyclica has developed, validated, patented and commercialized Ligand Express™, a cloud-based platform that screens small-molecule drugs against repositories of structurally-characterized proteins or ‘proteomes’ to determine polypharmacological profiles. Accordingly, Ligand Express™ identifies significant protein targets using an innovative structure-based and drug-centric technology, leverages artificial intelligence to determine the drug’s effect on these targets, and visualizes the predicted drug-protein interactome using bioinformatics and systems biology. The platform provides a unique panoramic view of a small-molecule, by identifying on- and off-target interactions that may be expected, as well as those that are unanticipated.
Why is this Valuable?
By understanding how a small-molecule drug will interact with all proteins in the body, Ligand Express™ augments scientific investigation by elucidating mechanism of action, prioritizing lead candidates, understanding side effects, as well as determining new uses for existing drugs. You can access our platform at ligandexpress.com.
Watch our video to see Ligand Express in action!
Structural Pharmacogenomics (Feature Being Integrated)
Genetic data holds remarkable insights into human health; however, scientists are still developing methods to best utilize this plethora of data. With the support of the Ontario Centres of Excellence and IBM, Cyclica drives actionable insights out of genetic data by integrating them within Ligand Express™ through a technology called Structural Pharmacogenomics (SPG). Using super computing, Cyclica has prepared a robust genetic database of single nucleotide polymorphisms (SNPs) and maps them to the protein structure. This mapping exercise allows researchers to quickly identify potential genetic variants that would impact small molecule binding (see image below) or are implicated in disease. Planned integration: Early 2019.
ADMET Prediction (Feature Being Integrated Early 2019)
A drug needs to do more than binding to a drug target; it also needs to have desirable pharmacological properties. Ligand Express™ is gaining a collection of predictive ADMET models built using a proprietary AI methodology to help translate small molecules into drugs. The technology has demonstrated enhanced predictive accuracy for generating QSAR models compared to traditional classifiers as seen in the validation note here. Understanding polypharmacology through Ligand Express™ and coupling that with ADMET Prediction will allow scientists to make efficient and informed decisions like never before. Planned integration: Early 2019.