GTP-Competitive Inhibitors of RAS Family Members

J. C. Hunter, N. S. Gray, K. D. Westover

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Early efforts to therapeutically target RAS focused away from the GTP-binding site because it was assumed that small molecule inhibitors could never compete with the picomolar binding affinity and micromolar cellular concentrations of GTP and achieve specificity for the RAS family members. Medicinal chemistry has evolved, providing new options for designing covalent compounds. Here, we review the theoretical basis for attempting to target the GTP-binding site of RAS using covalent chemistry and discuss proof-of-concept experiments.

Original languageEnglish (US)
Title of host publicationConquering RAS
Subtitle of host publicationFrom Biology to Cancer Therapy
PublisherElsevier Inc.
Pages155-174
Number of pages20
ISBN (Electronic)9780128035412
ISBN (Print)9780128035054
DOIs
StatePublished - Jan 1 2017

Keywords

  • Covalent inhibitor
  • G12C
  • Irreversible inhibitor
  • K
  • KRAS

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Hunter, J. C., Gray, N. S., & Westover, K. D. (2017). GTP-Competitive Inhibitors of RAS Family Members. In Conquering RAS: From Biology to Cancer Therapy (pp. 155-174). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-803505-4.00009-6