GTP-Competitive Inhibitors of RAS Family Members

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

doi:10.1016/B978-0-12-803505-4.00009-6

GTP-Competitive Inhibitors of RAS Family Members

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

Research output: Chapter in Book/Report/Conference proceeding › Chapter

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 language	English (US)
Title of host publication	Conquering RAS
Subtitle of host publication	From Biology to Cancer Therapy
Publisher	Elsevier Inc.
Pages	155-174
Number of pages	20
ISBN (Electronic)	9780128035412
ISBN (Print)	9780128035054
DOIs	https://doi.org/10.1016/B978-0-12-803505-4.00009-6
State	Published - Jan 1 2017

Keywords

Covalent inhibitor
G12C
Irreversible inhibitor
K
KRAS

ASJC Scopus subject areas

Medicine(all)

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10.1016/B978-0-12-803505-4.00009-6

Cite this

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KW - Irreversible inhibitor

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KW - KRAS

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SN - 9780128035054

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EP - 174

BT - Conquering RAS

PB - Elsevier Inc.

ER -

GTP-Competitive Inhibitors of RAS Family Members

Abstract

Keywords

ASJC Scopus subject areas

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