Small Molecule Drug Discovery as Nature Would Have Done It
Nuevolutions Chemetics® Technology:
- Small Molecule Lead Discovery Platform
- Fast and efficient screening of more than 1 billion real small molecules
- Huge chemical diversity in screening libraries
- Potent hits and a high quantity of hits
- SAR available directly from screening data
- A unique small molecule solution for tractable and intractable targets incl. PPIs
Rubik’s cube represents 43×1018 (billions of billions) possible permutations, yet mathematical algorithms has allowed it to be solved in 20 moves and the world record for doing this is only 6 seconds.
Unfortunately, no mathematical algorithm has similarly been devised for drug discovery, allowing drug candidates to be identified by a general and equally efficient methodology.
Today, brute force in Drug Discovery allows for the HTS screening of maximum 1-5 million compounds for the initial hit identification, followed by cumbersome and costly optimization. The process works for the easier targets, but remains costly and fail-prone in the delivery of clinical candidates for more challenging targets such as those engaged in pharmaceutically relevant Protein:Protein Interactions.
Nature approaches the problem of finding the best solutions by applying brute force, i.e. testing as many combinations as possible. Natural systems allow the testing of billions of combinations.
Nuevolution has established proprietary methods termed Chemetics® for producing DNA-tagged small molecule libraries, wherein the DNA-tag is used to encode the synthetic history and chemical structure of the small molecules produced in a split-and-mix synthesis process. The use of DNA offers a unique way of storing information. The DNA-tag provides essentially single-molecule detection by allowing amplification and sequencing for hit/lead identification from in vitro affinity screening of compound libraries in the size of billions of small molecules.
The technology has been successfully applied in partnerships with Merck & Co., Lexicon Pharmaceuticals, Novartis Pharma and Boehringer Ingelheim as well as internal Nuevolution lead discovery programs, to identify small molecule solutions for tractable as well as intractable targets including protein-protein interactions.
The Chemetics® technology enables identification of small molecule drug candidates by application of Nature’s method of brute force as elegantly as mathematical algoritms allows the efficient solution of Rubik’s cube.