2. Academic Validation
  3. Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90)

Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock protein 90 (Hsp90)

  • Bioorg Med Chem. 2013 Nov 15;21(22):7047-63. doi: 10.1016/j.bmc.2013.09.018.
Maria Gabriella Brasca 1,  Sergio Mantegani,  Nadia Amboldi,  Simona Bindi,  Dannica Caronni,  Elena Casale,  Walter Ceccarelli,  Nicoletta Colombo,  Anna De Ponti,  Daniele Donati,  Antonella Ermoli,  Gabriele Fachin,  Eduard R Felder,  Ronald D Ferguson,  Claudio Fiorelli,  Marco Guanci,  Antonella Isacchi,  Enrico Pesenti,  Paolo Polucci,  Laura Riceputi,  Francesco Sola,  Carlo Visco,  Fabio Zuccotto,  Gianpaolo Fogliatto
Affiliations

Affiliation

  • 1 Nerviano Medical Sciences S.r.l., Oncology, Viale Pasteur 10, 20014 Nerviano, MI, Italy. Electronic address: gabriella.brasca@nervianoms.com.
PMID: 24100158 DOI: 10.1016/j.bmc.2013.09.018
Abstract

Novel small molecule inhibitors of heat shock protein 90 (HSP90) were discovered with the help of a fragment based drug discovery approach (FBDD) and subsequent optimization with a combination of structure guided design, parallel synthesis and application of medicinal chemistry principles. These efforts led to the identification of compound 18 (NMS-E973), which displayed significant efficacy in a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed in vivo by typical modulation of known HSP90 client proteins, and with a favorable pharmacokinetic and safety profile.

Keywords

Anti-cancer agents; Fragment based drug discovery; Tumor cell proliferation inhibition.

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