Proteasome inhibitors with pyrazole scaffolds from structure-based virtual screening

Zachary Miller, Keun Sik Kim, Do Min Lee, Vinod Kasam, Si Eun Baek, Kwang Hyun Lee, Yan Yan Zhang, Lin Ao, Kimberly Carmony, Na Ra Lee, Shou Zhou, Qingquan Zhao, Yujin Jang, Hyun Young Jeong, Chang Guo Zhan, Wooin Lee, Dong Eun Kim, Kyung Bo Kim

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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.

Original languageEnglish
Pages (from-to)2036-2041
Number of pages6
JournalJournal of Medicinal Chemistry
Issue number4
StatePublished - Feb 26 2015

Bibliographical note

Publisher Copyright:
© 2015 American Chemical Society.

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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