PDZ Drug Discovery Platform™

Arbor Vita created the PDZ Drug Discovery Platform™, which is used to discover PDZ domains or PDZ proteins that have the ability to interact with PDZ Ligands (PL). The PDZ Drug Discovery Platform offers exciting novel targeting, with the potential to create a new paradigm in drug discovery by reducing time and costs for target validation and drug screening and by increasing the quality of drugs (i.e., fewer side effects) and the overall probability of success. The Platform is a focused and rational approach to drug discovery, utilizing a combination of public and proprietary bioinformatics tools in silico molecular modeling and virtual screening tools, properly folded proteins, laboratory information management and the company's high-throughput screening (HTS) PRISM Matrix™ assay. In preliminary screening, Arbor Vita has discovered over 1,200 novel interactions, each one a potential drug target.

Definitive PDZ Protein Reference Set

Arbor Vita has reduced the target discovery and validation process from months to days by creating a comprehensive, properly folded PDZ reference set. The reference set permits high-throughput screening for small-molecule drugs that will target any PDZ/PL interaction with specificity. Arbor Vita has leveraged existing technology in a focused and rational approach to create the PRISM Database: the PDZ/PL reference set for drug discovery. Using information from the Human Genome Project, Arbor Vita has cloned and expressed nearly all the known human PDZ protein domains (~250) into properly folded recombinant proteins to create a PDZ reference set. Arbor Vita has also created a comprehensive set of PLs and tested pair-wise combinations to create a reference set of PDZ/PL interactions. The proprietary PRISM Database contains all of Arbor Vita's experimental data including the PDZ and PDZ/PL reference sets.

Bioinformatics and In Silico Molecular Modeling

Arbor Vita has created a proprietary predictive bioinformatics tool that includes computer-based (in silico) molecular modeling that allows scientists to quickly assess the potential biological significance of each molecular interaction. Utilizing x-ray crystal structure information on PDZ proteins, Arbor Vita has developed an accurate and testable set of computer models for PDZ domains. Using the experimental data in the PRISM Database, models of PDZ/PL complexes are used to direct small-molecule screens. Analysis of the data from such screens will allow Arbor Vita to further refine the docking models to reflect small-molecule binding and validation of the in silico results can be accomplished using Arbor Vita's Matrix assay. To maximize value, the system is integrated with public and proprietary discovery research tools, relevant articles from the scientific literature, and other protein and nucleic acid databases.

Arbor Vita is also pioneering algorithms that permit biologists to conduct scientific queries in a more powerful, hypothesis-driven manner. These tools allow biologists without computer programming ability to generate and test ideas based on the most recent proprietary and public data. Combined with the power of the PDZ Drug Discovery Platform's biochemical assays, this bioinformatics and in silico approach makes it possible for Arbor Vita to complete target identification and validation processes rapidly.

The PRISM Matrix HTS™

The PRISM Matrix is a high throughput screen that uses properly folded human proteins to ensure that interactions identified via the PRISM Matrix HTS are true and relevant to actual biological systems. The PRISM Matrix HTS is rapidly scalable to meet both high-throughput therapeutic compound screening needs and partnership opportunities that may arise. The proprietary PRISM Matrix HTS quickly and accurately identifies novel interactions, titrates interactions to assess actual binding affinities and assesses the efficacy of potential lead compounds at blocking interactions. The PRISM Matrix HTS can be inexpensively automated with robotics, thus the capacity for expansion is virtually unlimited.