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compound diversity seting against various molecular targets

The research performed by the Lebedyeva Laboratory focuses on identifying hits for various targets using the molecular docking approach. The laboratory also specializes in organic synthesis, providing small molecules based on predicted bioactivity profiles. The “screen less, get more hits of better quality” paradigm has been employed to develop small compound diversity sets with 3,000-5,000 compounds per set. Compounds with reactive and undesirable functional groups, compounds potentially unstable in acidic conditions, as well as some imines and pyrimidine-triones have been eliminated from these sets. These sets have been tested for hit identification on several targets such as Akt1, Bcl-xL, Hsp90, the mixedlineage leukemia protein, human nCDase, WDR5, SUV39H2, and TREM1. All compounds in the diversity sets belong to commercially available sources. Once lead compounds have been identified, the Lebedyeva Laboratory provides lead optimization. Leads from commercially available compound libraries often require further optimization that would induce increased potency, lower toxicity, improved solubility, novelty, etc. Thus, the Lebedyeva Laboratory provides “hit-to-lead,” early-stage drug discovery using computational screening of customized small compound diversity sets against various molecular targets. Research on the synthesis of bioactive compounds has resulted in a book chapter (Top Heterocycl Chem. 2015, pages 1–47) and several manuscripts (J Mater Chem B. 2015, 3(43): 8492-8; Bioorg Med Chem. 2015, 23(15):5056-60; Tetrahedron Lett. 2015, 56(48):6653-5; Org Biomol Chem. 2015, 13(15):4399-403).