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Dual-State KRAS G12C Inhibitors as Emerging Therapeutics for Brain and Lung Metastases.

ACS medicinal chemistry letters 2025 Vol.16(12) p. 2389-2391

Renner AC, Kargbo RB

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New-generation KRAS G12C inhibitors demonstrate enhanced activity in both peripheral and central nervous system malignancies.

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APA Renner AC, Kargbo RB (2025). Dual-State KRAS G12C Inhibitors as Emerging Therapeutics for Brain and Lung Metastases.. ACS medicinal chemistry letters, 16(12), 2389-2391. https://doi.org/10.1021/acsmedchemlett.5c00662
MLA Renner AC, et al.. "Dual-State KRAS G12C Inhibitors as Emerging Therapeutics for Brain and Lung Metastases.." ACS medicinal chemistry letters, vol. 16, no. 12, 2025, pp. 2389-2391.
PMID 41403995

Abstract

New-generation KRAS G12C inhibitors demonstrate enhanced activity in both peripheral and central nervous system malignancies. Frontier Medicines' pyridopyrimidines and Novartis's spiro-indazole inhibitor (opnurasib) overcome resistance mechanisms by targeting both GDP- and GTP-bound KRAS states. Their blood-brain barrier permeability and synergy with immune checkpoint inhibitors represent a transformative advance for KRAS-driven cancers, especially metastatic nonsmall cell lung cancer (NSCLC).

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