GUELPH, Ontario ¿ Computer-aided drug design holds the promise of producing therapeutically active molecules more efficiently than the traditional compound library synthesis and screen methodologies. However, not every computational drug design technology is created equal.
As Barbara Fanning, director of business development at Nanodesign Inc., told BioWorld International, the company is enhancing and accelerating the drug-discovery and development process through application of its Evolution ary Molecular Design (EMD) technology.
EMD represents a major improvement over existing methods, such as structure-based design, combinatorial chemistry, computational methods and traditional medicinal chemistry, the company said, because it utilizes simulated evolutionary processes to solve complex problems of drug design and optimization. EMD uses information about the structure and biological activity of known pharmacologically active compounds as criteria to rapidly generate new structures that share and improve upon the properties of the original compounds.
The objective of the EMD process is to develop novel compounds with a high probability of targeted biological activity, Fanning said.
The design process begins with the construction of virtual receptors that can identify the structural features of ligands that are required for binding with specific biological receptors.
Virtual receptors are created through an iterative process using structural and biological activity data from known active and inactive compounds. Virtual receptors can be used to test novel compounds for binding affinity, reducing the need for costly and time-consuming synthesis and biological screening. More importantly, as virtual receptors are constructed, features that are essential for high-affinity binding are identified. During construction, physicochemical properties and synthetic feasibility are estimated computationally for each intermediate structure. The conformational stability of each structure also is evaluated.
Those parameters are used in combination with testing against virtual receptors to calculate a fitness score during the evolution of the design. At the completion of this process the selected compound designs are available for synthesis, testing and further commercial development.
Using EMD, Nanodesign has completed the design and synthesis of new chemical classes of orally available antiestrogens for the treatment of breast cancer, Fanning said. ¿Achieving synthesis of these molecules, through the use of independent contractors, is the first demonstration of EMD as a reliable and predictive design tool.¿¿
Compounds have entered a multi-tiered biological testing program to confirm the novel computational process achieved the desired therapeutic activity profile.
Nanodesign scientists also have determined that some of the new chemical entities warrant analysis and testing for anti-angiogenic activity. Initial results from biological testing are consistent with expectations, and results for both activity profiles are expected soon.
The new platform technology also is being applied to several areas of oncology.
Nanodesign is actively negotiating with pharmaceutical companies for collaborative research projects, and will be seeking to license its portfolio of new chemical entities at an early stage for further development.