Ultimate – a unique online marketplace for drug discovery The pharmaceutical industry has on an ongoing quest for new compounds that can become drug candidates against various diseases. To facilitate this and help scientists and researchers working on drug discovery, a European project has developed an innovative platform. Health © Shawn Hempel, Shutterstock During the early phase of drug discovery, after identification of the therapeutic target, researchers have to select the most appropriate candidate molecules that inhibit or stimulate the activity of the target. This means they have to choose from over 30 million molecules available ‘off-the-shelf’ from suppliers. This is not an easy task and it only offers already synthesised compounds. A database of virtual compounds The EU-funded ULTIMATE project developed a proprietary chemical database. In addition to ‘off-the-shelf’ chemicals, it contains virtual compounds that are predicted to be synthesisable. “Our goal is to create virtual compounds of high pharmaceutical interest, which can be synthesised in 2-6 weeks for a reasonable price,″ explains project coordinator, CEO and co-founder of Mcule, Róbert Kiss. Following close collaboration with chemical suppliers, experts and ULTIMATE partners Mcule produced a key innovation: an artificial chemist algorithm, which can generate virtual compounds using chemicals from known supplier partners and selected robust chemical reactions. The virtual compounds in the ULTIMATE database are generated from a starting chemical point and are of exceptionally high novelty and quality. This offers scientists the opportunity to work with unprecedented molecules of high patentable potential and identify drug-like compounds that didn’t previously exist. Database features The ULTIMATE database can be accessed through the Mcule company web-based platform. Currently, it contains 500 million purchasable compounds with a delivery time of up to 6 weeks. The Mcule platform offers search tools for a subscription fee alongside molecular modelling tools that enable scientists to identify compounds based on the 3D structure and function of their target. Using the ULTIMATE database, scientists can perform molecular docking of various compounds on therapeutic targets to ensure that critical interaction takes place. They can exploit different chemical scaffolds, as well as test the physicochemical properties and the toxicity of the resultant compounds. This allows researchers to prioritise the compounds with the highest efficiency and reject problematic ones with high toxicity, selectivity or pharmacokinetic issues. Collectively, the comprehensive set of drug discovery tools enables scientists to build up complex workflows like LEGO bricks. Advantages of the ULTIMATE database The ULTIMATE large chemical space constitutes a very useful tool for pharmaceutical and biotech companies by increasing their chances to effectively identify novel compounds for diseases, reducing time and cost. In addition, it provides an easy-to-use chemical web shop that can be seamlessly integrated with the in-house platform of the pharma companies. The online platform offers automated compound selection and quote calculation. The first version of the ULTIMATE database and the platform are completed. Following successful beta testing, partners plan to commercially launch the platform and make it publicly accessible. They also envisage incorporation of additional unique solutions such as biological data handling and analysis. With a view to the future, Kiss is confident that “the ULTIMATE database will speed up small-molecule drug discovery and help to find effective treatment options for different types of cancers or neurodegenerative diseases, such as Alzheimer’s disease.″ Keywords ULTIMATE, compounds, database, chemical, platform, drug discovery, pharmaceutical, toxicity
