PRO_SELECT: combining structure-based drug design and array-based chemistry for rapid lead discovery. 2. The development of a series of highly potent and selective factor Xa inhibitors.

John W Liebeschuetz; Stuart D Jones; Phillip J Morgan; Chris W Murray; Andrew D Rimmer; Jonathan M E Roscoe; Bohdan Waszkowycz; Pauline M Welsh; William A Wylie; Stephen C Young; Harry Martin; Jacqui Mahler; Leo Brady; Kay Wilkinson

doi:10.1021/jm010944e

PubMed · 11881991

PRO_SELECT: combining structure-based drug design and array-based chemistry for rapid lead discovery. 2. The development of a series of highly potent and selective factor Xa inhibitors.

John W Liebeschuetz·Stuart D Jones·Phillip J Morgan·Chris W Murray·Andrew D Rimmer·Jonathan M E Roscoe·Bohdan Waszkowycz·Pauline M Welsh·William A Wylie·Stephen C Young·Harry Martin·Jacqui Mahler·Leo Brady·Kay Wilkinson

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Abstract

In silico screening of combinatorial libraries prior to synthesis promises to be a valuable aid to lead discovery. PRO_SELECT, a tool for the virtual screening of libraries for fit to a protein active site, has been used to find novel leads against the serine protease factor Xa. A small seed template was built upon using three iterations of library design, virtual screening, synthesis, and biological testing. Highly potent molecules with selectivity for factor Xa over other serine proteases were rapidly obtained.

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Animals Benzamidines Combinatorial Chemistry Techniques Drug Design Enzyme Inhibitors Factor Xa Inhibitors Humans Models, Molecular Protein Conformation Rats Structure-Activity Relationship Journal Article

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John W Liebeschuetz, Stuart D Jones, Phillip J Morgan, Chris W Murray, Andrew D Rimmer, Jonathan M E Roscoe, Bohdan Waszkowycz, Pauline M Welsh, William A Wylie, Stephen C Young, Harry Martin, Jacqui Mahler, Leo Brady, Kay Wilkinson. 2002-03-14. PRO_SELECT: combining structure-based drug design and array-based chemistry for rapid lead discovery. 2. The development of a series of highly potent and selective factor Xa inhibitors.. https://doi.org/10.1021/jm010944e

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