We performed a virtual screen of ∼340 000 small molecules against the active site of proteasomes followed by in vitro assays and subsequent optimization, yielding a proteasome inhibitor with pyrazole scaffold. The pyrazole-scaffold compound displayed excellent metabolic stability and was highly effective in suppressing solid tumor growth in vivo. Furthermore, the effectiveness of this compound was not negatively impacted by resistance to bortezomib or carfilzomib.
|Number of pages||6|
|Journal||Journal of Medicinal Chemistry|
|State||Published - Feb 26 2015|
Bibliographical notePublisher Copyright:
© 2015 American Chemical Society.
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery