2. Academic Validation
  3. Discovery of a novel series of Notch-sparing gamma-secretase inhibitors

Discovery of a novel series of Notch-sparing gamma-secretase inhibitors

  • Bioorg Med Chem Lett. 2008 Jul 15;18(14):4232-6. doi: 10.1016/j.bmcl.2008.05.064.
Anthony Kreft 1,  Boyd Harrison,  Suzan Aschmies,  Kevin Atchison,  David Casebier,  Derek C Cole,  George Diamantidis,  John Ellingboe,  Diane Hauze,  Yun Hu,  Donna Huryn,  Mei Jin,  Dennis Kubrak,  Peimin Lu,  Joseph Lundquist,  Charles Mann,  Robert Martone,  William Moore,  Aram Oganesian,  Alex Porte,  Dave R Riddell,  June Sonnenberg-Reines,  Joseph R Stock,  Shaiu-Ching Sun,  Erik Wagner,  Kevin Woller,  Zheng Xu,  Hua Zhou,  J Steven Jacobsen
Affiliations

Affiliation

  • 1 Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA. [email protected]
PMID: 18556202 DOI: 10.1016/j.bmcl.2008.05.064
Abstract

Using a cell-based assay, we have identified a new series of Notch-sparing gamma-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved gamma-secretase inhibitory potency and Notch-sparing selectivity.

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