Forward Engineering™ is able to discover new chemical entities (NCEs) more quickly, at a lower cost, and with less risk than traditional discovery methods.
Identifying the topological signature responsible for activity via MT based on a few (typically 25-30) structurally diverse compounds is analogous to determining what pieces fit the outer edge of a jigsaw puzzle. With these few compounds, the goal is not to try to populate the entire puzzle with ALL the pieces, just the outer edges. Hence, determining the topological signature and capturing the signature in the model "fills out" the outer edges of the puzzle. Then, "other pieces" can be identified to fill the interior of the puzzle.
Based on previous work performed by Medisyn, the "other pieces" typically include novel compounds in new chemical classes that have the same topological signature as the "pieces" used to form the outer edge. Along with natural and synthesized compounds, MT is able to screen billions of compounds efficiently from the vast domain of virtual space estimated to contain as many as 1063 virtual compounds, whereas high throughput screening is limited to approximately 25 million existing compounds. Furthermore, high throughput screening requires wet chemistry testing of 100,000 to several million compounds to get to useful qualified leads, while MT requires testing of only around 100 compounds to achieve the desired efficacy and ADME/TOX characteristics. This overall efficiency allows MT to screen millions of molecules in the same amount of time it takes 3-D targeted design methodologies to analyze a few dozen.
This technology is a powerful tool in the discovery process as the training sets can be designed to identify molecules with a wide range of properties. For example, molecular topology has the proven ability to identify compounds based on smell, taste, and mutagenicity (tendency to cause genetic mutations). Medisyn has developed a diverse range of ADME/Tox filters that are designed to screen compounds in parallel for safety and drug-like effectiveness prior to experimental testing. This unique capability helps mitigate the risk of late-stage failure of lead compounds often encountered during drug development. The design of NCEs can be undertaken using the activity profile captured by the predictive model to yield patentable novel compounds for further development. Thus, the core features of MT are speed, low cost, risk mitigation, and NCE discovery.
While not every compound identified is necessarily biologically active, a validated model can achieve 50-85% predictive accuracy for useful active molecules (with multiple required properties), versus 0.1% of fuzzy hits with activity using High Throughput Screening techniques. Therefore, MT is not a "fishing expedition" but rather careful selection of "active" molecules based on the same topological signature. Consequently, Medisyn's Forward Engineering™ technology is uniquely equipped to deal with the challenges encountered during discovery of novel compounds.