Iryna O. Lebedyeva and Thomas Albers
Department of Chemistry and Physics, Augusta University, Augusta, GA, USA
The "screen less, get more hits of better quality" paradigm has been employed to develop small 3,000-5,000 compound diversity sets. In these sets compounds with reactive and undesirable functional groups, compounds potentially unstable at acidic condition compounds, some imines and pyrimidine-triones have been eliminated. These sets have been tested for hit identification on several targets such as Akt1, Bcl-xL, and Hsp90, the mixed-lineage leukemia protein, human nCDase, WDR5, SUV39H2, TREM1. All the compounds in the diversity sets belong to the commercially available sources.
Once Lead compounds have been identified, the Laboratory of Medicinal Chemistry at Augusta University provides Lead optimization. Leads from commercially available compound libraries often require further optimization that would lead to increased potency, lower toxicity, improved solubility, novelty etc. We modify known compounds into novel chemical entities with improved properties.
Thus, our laboratory provides Hit-to-Lead early stage drug discovery using computational screening of customized small compound diversity sets against various molecular targets.
Our early stage drug design concept lies in the following steps: