Targeting mutant KRAS for anticancer therapeutics: A review of novel small molecule modulators

Yuanxiang Wang, Christine E. Kaiser, Brendan Frett, Hong Yu Li

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


The RAS proteins play a role in cell differentiation, proliferation, and survival. Aberrant RAS signaling has been found to play a role in 30% of all cancers. KRAS, a key member of the RAS protein family, is an attractive cancer target, as frequent point mutations in the KRAS gene render the protein constitutively active. A number of attempts have been made to target aberrant KRAS signaling by identifying small molecule compounds that (1) are synthetic lethal to mutant KRAS, (2) block KRAS/GEF interactions, (3) inhibit downstream KRAS effectors, or (4) inhibit the post-translational processing of RAS proteins. In addition, inhibition of novel targets outside the main KRAS signaling pathway, specifically the cell cycle related kinase PLK1, has been shown have an effect in cells that harbor mutant KRAS. Herein we review the use of various high-throughput screening assays utilized to identify new small-molecule compounds capable of targeting mutant KRAS-driven cancers.

Original languageEnglish (US)
Pages (from-to)5219-5230
Number of pages12
JournalJournal of Medicinal Chemistry
Issue number13
StatePublished - Jul 11 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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