2. Academic Validation
  3. Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors

Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors

  • Bioorg Med Chem Lett. 2009 Dec 1;19(23):6784-7. doi: 10.1016/j.bmcl.2009.09.081.
Theodore C Jessop 1,  James E Tarver,  Marianne Carlsen,  Amy Xu,  Jason P Healy,  Alexander Heim-Riether,  Qinghong Fu,  Jerry A Taylor,  David J Augeri,  Min Shen,  Terry R Stouch,  Ronald V Swanson,  Leslie W Tari,  Michael Hunter,  Isaac Hoffman,  Philip E Keyes,  Xuan-Chuan Yu,  Maricar Miranda,  Qingyun Liu,  Jonathan C Swaffield,  S David Kimball,  Amr Nouraldeen,  Alan G E Wilson,  Ann Marie Digeorge Foushee,  Kanchan Jhaver,  Rick Finch,  Steve Anderson,  Tamas Oravecz,  Kenneth G Carson
Affiliations

Affiliation

  • 1 Lexicon Pharmaceuticals, Princeton, NJ 08540, United States. tjessop@lexpharma.com
PMID: 19836232 DOI: 10.1016/j.bmcl.2009.09.081
Abstract

A series of deoxycytidine kinase inhibitors was simultaneously optimized for potency and PK properties. A co-crystal structure then allowed merging this series with a high throughput screening hit to afford a highly potent, selective and orally bioavailable inhibitor, compound 10. This compound showed dose dependent inhibition of deoxycytidine kinase in vivo.

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