Insights into fourth generation selective inhibitors of (C797S) EGFR ...
Jun 21, 2023 · Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism. This review covers the fourth-generation EGFR-TKIs' most recent design with their essential binding interactions, the clinical difficulties, and the potential outcomes of treating ...
Recent advances of novel fourth generation EGFR inhibitors in ...
Jan 5, 2023 · This paper investigates the advances in overcoming C797S mutation resistance reported in literature since 2021, including the newly developed fourth-generation EGFR-TKIs, PROTAC-based drug design, and the combination strategy, etc.
Advancements in fourth-generation EGFR TKIs in EGFR-mutant …
Nov 1, 2024 · Fourth-generation allosteric EGFR-TKIs are orally bioavailable, thiazole amid-based, EGFR-mutant selective agents that hold the promise of targeting EGFR-activating mutations and simultaneously overcoming C797S-mediated resistance, regardless of T790M, through a selective bond to an allosteric site that alters EGFR conformation, hence bypassing ...
The reversible fourth-generation EGFR tyrosine kinase ... - PubMed
Feb 3, 2022 · Here, we report the discovery and preclinical efficacy of OBX02-011, a reversible fourth-generation EGFR TKI that overcomes the EGFR C797S mutation. Compared to approved EGFR TKIs, OBX02-011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation.
Resistance is futile with fourth-generation EGFR inhibitors
Apr 14, 2022 · Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have revolutionized the treatment of EGFR-mutant non-small cell lung cancer; however, secondary resistance limits their...
Abstract 4476: BI-732, a novel fourth-generation EGFR-TKI, …
Apr 4, 2023 · Acquired EGFR-C797S mutation is the most common on-target resistance mechanism to osimertinib in first- and second-line settings, and there are currently no approved targeted therapies. We aimed to evaluate the efficacy of BI-732, a fourth-generation EGFR-TKI developed to overcome the C797S mutation.
《自然·癌症》：第四代EGFR TKI临床开发迈出关键一步
May 4, 2022 · 总体而言，jbj-09-063是具有突出临床潜力第四代egfr抑制剂，可作为单药或与egfr-tkis联用来治疗egfr突变肺癌，期待其早日进入临床，弥补egfr-tkis治疗的不足。
Potential Utility of a 4th-Generation EGFR-TKI and Exploration of ...
Jun 25, 2024 · To overcome both the T790M and C797S mutations, novel 4G EGFR-TKIs are now under early clinical development. In this study, we evaluated the efficacy of a 4G EGFR-TKI in the treatment of lung cancer with EGFR mutation as well as …
MA07.08 JIN-A02, a Highly Effective 4th Generation EGFR-TKI, …
Aug 8, 2022 · JIN-A02 is a novel, orally available, fourth-generation EGFR tyrosine kinase inhibitor (TKI) targeting C797S mutation and has demonstrated potent anti-tumor activity in preclinical models of double- or triple-mutant EGFR (ex19del/T790M or ex19del/T790M/C797S).
Binding Thermodynamics of Fourth-Generation EGFR Inhibitors …
Dec 6, 2023 · Our findings reveal that BLU-945 and CH7233163 exhibit binding affinities to both EGFR DM and EGFR TM stronger than those of erlotinib, corroborating experimental data. We identified K745 and T854 as the key residues in the binding of fourth-generation EGFR TKIs.