|23:00 CST (Shanghai),||16:00 CET (Berlin),||11:00 am EDT (New York)|
Virtual-screening enables searching and ranking millions of virtual molecules at a low cost. A key aspect for success is to search synthesizable virtual molecules and to provide a representative search space covering interesting chemical space. The exploration of explicitly enumerated molecules is limited due to computational resources and search times. Therefore, we investigate the exploration of the AZ-virtual chemistry space using FTrees-FS, which does not require any enumeration of molecules, and compare results to explicitly enumerated libraries. The definition of the AZ-virtual chemistry space provides access to a large and diverse chemical space ready for synthesis allowing for quick turn-around times and synthesis.
How do you start a research program and advance it with the limited funds you have? This is a common problem we all face whether you are in industry or in academia. In drug discovery if you don't have a way to know what compounds you should buy/make then your chances of success are the same as buying a lottery ticket. And even if you have a promising hit/lead compound, how will you improve it? How much should you improve it? And to what end? A publication, patent filing, grant application? In this webinar Dr. Morales will cover these points, foundations to tackle obstacles and make decisions to start and advance research projects.
The challenges associated with anti-infective drug-discovery programmes can be tackled by combining antibacterial screening with several established and unprecedented hit-identification strategies in parallel. This approach will be illustrated using two targets: The first is the enzyme DXS from the methyl erythritol phosphate pathway, which is essential for pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum for the biosynthesis of the essential isoprenoid precursors, but absent in humans. We identified inhibitors with promising in vitro and anti-infective activity (M. tuberculosis and P. falciparum) using a number of hit-identification strategies, namely ligand- and structure-based virtual screening, phage display, dynamic combinatorial chemistry and de novo fragment-based design.
The second target is a vitamin transporter from the energy-coupling factor (ECF) class, which consist of an energizing module and a substrate-binding protein (S-component). Different S-components can interact with the same energizing module. We designed and synthesized substrate analogues with high affinity (Kd = 4–660 nM) and confirmed the predicted binding mode. A structure-based virtual screening campaign provided us with the first allosteric inhibitors of the transporter for folate, which are not cytotoxic and show promising antibacterial (S. aureus and S. pneumoniae) activity.
As you know Enamine and BioSolveIT joined forces to build the world's largest space of available compounds. In January 2018 we published the first version and packaged it with an ultra-fast search engine as well as with the most convenient UI called REAL Space Navigator. We also stated that the 650 million compounds therein would be just the beginning. So now – just a few months later – we are proud to announce version 2:
REAL Space allows for efficient hit exploration, from finding previously unknown analogues to scaffold hopping. The chemical space encoded with more than 139 Enamine synthesis protocols and upgraded in-stock building blocks, provides an escape from availability bias of current stock screening collections towards IP free areas. Compounds selected from this space will be synthesized in 3-4 weeks with an exceptional success rate of 80% and above.
In this webinar we explain the genesis and composition of the space as well as the search magic to access this vast resource. We also demonstrate the user-friendly graphical interface. Join us to learn more about this exciting joint venture. Almost 3.8 billion virtual molecules that become real on demand are a resource that is simply too valuable to miss...