Aim: Design, synthesis and evaluation of a series of 7-imidazolylalkanamido-1-carboxylalkylbenzodiazepine farnesyltransferase (FTase) inhibitors.
Methods And Results: Coupling of imidazolylalkylcarboxylic acids and 1-substituted 7-aminobenzodiazepines (5a-5c) yielded 10 new compounds (6-12, 16-18) which were biologically tested against FTase using scintillation proximity assay method.
Conclusion: Five target compounds were found to be potential farnesyltransferase inhibitors.
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FGTI-2734 Inhibits ERK Reactivation to Overcome Sotorasib Resistance in KRAS G12C Lung Cancer.
J Thorac Oncol
November 2024
Department of Pharmacology and Toxicology and Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, Virginia. Electronic address:
Introduction: KRAS G12C targeted therapies, such as sotorasib, represent a major breakthrough, but overall response rates and progression-free survival for patients with KRAS G12C lung cancer are modest due to the emergence of resistance mechanisms involving adaptive reactivation of ERK, which requires wild-type HRAS and NRAS membrane localization.
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