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- W2425374734 endingPage "7633" @default.
- W2425374734 startingPage "7611" @default.
- W2425374734 abstract "Currently, the creation of class- and isoform-selective modulators of biologically important targets is a particularly challenging problem because different isoforms within a protein family often show striking similarity in spatial quaternary structure, especially at the catalytic sites or binding pockets. Therefore, an understanding of both the precise three-dimensional structure of the target protein and the mechanisms of action of modulators is important for developing more effective and selective agents. In this Perspective, we discuss currently available rational design strategies for obtaining class- and isoform-selective inhibitors and we illustrate these strategies with the aid of specific examples from the recent literature. The strategies covered include: (1) target-derived (-dependent) de novo drug discovery methodologies, and (2) follow-on derivatization approaches from initially identified active molecules (hit-to-lead and lead-to-candidate efforts). We also comment on prospects for further development and integration of strategies to achieve target-specific or isoform-selective inhibition." @default.
- W2425374734 created "2016-06-24" @default.
- W2425374734 creator A5035724323 @default.
- W2425374734 creator A5044997693 @default.
- W2425374734 creator A5052910102 @default.
- W2425374734 creator A5059468550 @default.
- W2425374734 date "2015-07-01" @default.
- W2425374734 modified "2023-10-18" @default.
- W2425374734 title "Strategies for the Discovery of Target-Specific or Isoform-Selective Modulators" @default.
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