2. Academic Validation
  3. A series of novel, potent, and selective histone deacetylase inhibitors

A series of novel, potent, and selective histone deacetylase inhibitors

  • Bioorg Med Chem Lett. 2006 Dec 1;16(23):5948-52. doi: 10.1016/j.bmcl.2006.09.002.
Philip Jones 1,  Sergio Altamura,  Prasun K Chakravarty,  Ottavia Cecchetti,  Raffaele De Francesco,  Paola Gallinari,  Raffaele Ingenito,  Peter T Meinke,  Alessia Petrocchi,  Michael Rowley,  Rita Scarpelli,  Sergio Serafini,  Christian Steinkühler
Affiliations

Affiliation

  • 1 IRBM/Merck Research Laboratories, Via Pontina km 30,600, 00040 Pomezia, Italy. philip_jones@merck.com
PMID: 16987657 DOI: 10.1016/j.bmcl.2006.09.002
Abstract

Histone deacetylase (HDAC) inhibitors offer a promising strategy for Cancer therapy and the first generation HDAC inhibitors are currently in clinical trials. A structurally novel series of HDAC inhibitors based on the natural cyclic tetrapeptide Apicidin is described. Selected screening of the sample collection looking for L-2-amino-8-oxodecanoic acid (L-Aoda) derivatives identified a small acyclic lead molecule 1 with the unusual ketone zinc binding group. SAR studies around this lead resulted in optimization to potent, low molecular weight, selective, non-hydroxamic acid HDAC inhibitors, equipotent to current clinical candidates.

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