| Literature DB >> 24100158 |
Maria Gabriella Brasca1, 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.
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.Entities:
Keywords: Anti-cancer agents; Fragment based drug discovery; Tumor cell proliferation inhibition
Mesh：
Substances：
Year: 2013 PMID： 24100158 DOI： 10.1016/j.bmc.2013.09.018
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641