Unlocking Synergy of Parts: FBL, Fragment-Based Library, for Drug Discovery

Oct. 20, 2010 - PRLog -- Fragment-based drug discovery truly unlocks synergy of parts by finding highly diverse and small ligands that ever increase their binding efficiency and maximize bioavailability once joined in a new molecule.



FBDD is also great compliment to any HTS campaign for enzyme targets as it aids early hit discovery and optimization when data from both screening approaches is combined and compared. Fragment library screen is always target specific in fit being comprised of minimum pharmacophores. FBDD unites the knowledge of traditional screening approaches with the logic of structure-based design. If available, any structural parts match between HTS and FBDD hits is a good foundation for preliminary SAR.



TimTec Fragment-Based Library, FBL, gathers structurally diverse ligands with well suited chemical-physical properties for FBDD screening. Compounds are delivered in dry form in custom milligram or micromolar amounts and as freshly prepared DMSO solution aliquots. One of the preferred concentrations for FBDD is up to 1.5mM with small volume (1-25-30-50uL) per well. Compound selection criteria for FBDD overlaps in chemical-physical properties and screening techniques, yet is more encompassing and specific, than compound selection criteria for the Rule of Three and, so called, Reduced Complexity Criteria.



Fragment-Based Drug Discovery has been gaining more and more attention since mid 1990s, the year when the SAR-by-MNMR technology is developed at Abbott. Number of the most recent technological advancements makes FBDD very approachable part of HTS campaigns. Fragment screening techniques would include protein NMR, small-molecule NMR, X-ray crystallography, thermal shift assays, surface plasmon resonance, and high concentration activity assays.



Small in size FBDD libraries furnish vast chemical space design combinations in building drugs from small molecular pieces. Favorable structure-based approach can be applied very early in fragments optimization to decrease and/or eliminate undesirable structural characteristics to boost in vivo safety and minimize number of to-be-synthesized lead candidates. Optimization strategies of linking, growing, and merging may not only identify lead candidates right away, but also identify desirable scaffolds in HTS compounds databases.

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TimTec, evolved from a venture started by the Zelinsky Institute of Organic Chemistry (ZIOC) in Russia in the late 1980’s. Tremendous growth opportunities in the field of biological screening prompted us to establish operations in Europe and the US.