Interaction and molecular dynamics simulation study of Osimertinib (AstraZeneca 9291) anticancer drug with the EGFR kinase domain in native protein and mutated L844V and C797S
Sign Up to like & getrecommendations! Published in 2019 at "Journal of Cellular Biochemistry"
DOI: 10.1002/jcb.28575
Abstract: Targeted therapy is a novel, promising approach to anticancer treatment that endeavors to overcome drug resistance to traditional chemotherapies. Patients with the L858R mutation in epidermal growth factor receptor (EGFR) respond to the first generation… read more here.
Keywords: egfr; c797s; kinase; interaction molecular ... See more keywords
Vorinostat combined with brigatinib overcomes acquired resistance in EGFR-C797S-mutated lung cancer.
Sign Up to like & getrecommendations! Published in 2021 at "Cancer letters"
DOI: 10.1016/j.canlet.2021.03.022
Abstract: The development of a new generation of tyrosine kinase inhibitors (TKIs) has improved the treatment response in lung adenocarcinomas. However, acquired resistance often occurs due to new epidermal growth factor receptor (EGFR) mutations. In particular,… read more here.
Keywords: egfr; c797s; vorinostat; acquired resistance ... See more keywords
Mechanistic Modeling of Lys745 Sulfonylation in EGFR C797S Reveals Chemical Determinants for Inhibitor Activity and Discriminates Reversible from Irreversible Agents
Sign Up to like & getrecommendations! Published in 2023 at "Journal of Chemical Information and Modeling"
DOI: 10.1021/acs.jcim.2c01586
Abstract: Targeted covalent inhibitors hold promise for drug discovery, particularly for kinases. Targeting the catalytic lysine of epidermal growth factor receptor (EGFR) has attracted attention as a new strategy to overcome resistance due to the emergence… read more here.
Keywords: sulfonylation; activity; mechanics; egfr ... See more keywords
Conformational Constrained 4-(1-Sulfonyl-3-indol)yl-2-phenylaminopyrimidine Derivatives as New Fourth-Generation Epidermal Growth Factor Receptor Inhibitors Targeting T790M/C797S Mutations.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00168
Abstract: Tertiary C797S mutation of epidermal growth factor receptor (EGFR)-mediated resistance in non-small-cell-lung-cancer (NSCLC) patients is still an unmet clinical need. Several classes of adenosine 5'-triphosphate-competitive or allosteric EGFRT790M/C797S inhibitors and degraders have been developed, but… read more here.
Keywords: c797s; factor receptor; epidermal growth; growth factor ... See more keywords
Optimization of Brigatinib as New Wild-Type Sparing Inhibitors of EGFRT790M/C797S Mutants.
Sign Up to like & getrecommendations! Published in 2022 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.1c00555
Abstract: A series of brigatinib derivatives were designed and synthesized as new potent and selective EGFRT790M/C797S inhibitors. One of the most potent and selective compounds 18k strongly suppressed the EGFRL858R/T790M/C797S and EGFR19Del/T790M/C797S kinases with IC50 values… read more here.
Keywords: egfrt790m c797s; brigatinib new; optimization brigatinib; c797s ... See more keywords
Design, Synthesis, and Biological Evaluation of Novel EGFR PROTACs Targeting Del19/T790M/C797S Mutation.
Sign Up to like & getrecommendations! Published in 2022 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.1c00645
Abstract: The tertiary epidermal growth factor receptor (EGFR) C797S mutation predominates in the acquired mutational resistance in cancer patients to third-generation EGFR inhibitors. Small-molecule inhibitors targeting the EGFR C797S mutation have been developed with good efficiency.… read more here.
Keywords: t790m c797s; egfr; c797s; c797s mutation ... See more keywords
Addressing the Osimertinib Resistance Mutation EGFR-L858R/C797S with Reversible Aminopyrimidines.
Sign Up to like & getrecommendations! Published in 2023 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.2c00514
Abstract: Drug resistance mutations emerging during the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) inhibitors represent a major challenge in personalized cancer treatment and require constant development of new inhibitors.… read more here.
Keywords: l858r c797s; resistance; egfr l858r; mutation ... See more keywords
Inhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S††Electronic supplementary information (ESI) available. CCDC 1876852. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c9sc03445e
Sign Up to like & getrecommendations! Published in 2019 at "Chemical Science"
DOI: 10.1039/c9sc03445e
Abstract: We present inhibitors of drug resistant mutants of EGFR including T790M and C797S. In addition, we present the first X-ray crystal structures of covalent inhibitors in complex with C797S-mutated EGFR to gain insight into their… read more here.
Keywords: osimertinib resistant; c797s; t790m c797s; esi ... See more keywords
Abstract 4005: PH009-1, a highly potent and selective fourth-generation EGFR-TKI overcoming EGFR common mutations and T790M/C797S-mediated resistance in NSCLC
Sign Up to like & getrecommendations! Published in 2023 at "Cancer Research"
DOI: 10.1158/1538-7445.am2023-4005
Abstract: Background: Epidermal growth factor receptor (EGFR) activating mutations have been reported in 10-50% of patients with non-small cell lung cancer (NSCLC). The common mutations, ex19del (D) and L858R (L) substitution, are sensitive to first- and… read more here.
Keywords: common mutations; egfr tki; c797s; generation egfr ... See more keywords
Abstract 4016: Discovery of a small-molecule EGFR inhibitor that can potently target various EGFR mutants, including C797S mutant, in vitro and in vivo
Sign Up to like & getrecommendations! Published in 2023 at "Cancer Research"
DOI: 10.1158/1538-7445.am2023-4016
Abstract: EGFR is one of receptor tyrosine kinases (RTKs) and, upon ligand binding, turns on the downstream signals that include oncogenic RAS/MEK/ERK, PI3K/AKT/mTOR, and JAK/STAT pathways. EGFR gene mutations, such as Exon 19 deletion (Del19) and… read more here.
Keywords: small molecule; egfr mutants; inhibitor; t790m ... See more keywords
Abstract 5006: Discovery of novel heterobifunctional degraders of mutant EGFR proteins for NSCLCs harboring various EGFR mutations
Sign Up to like & getrecommendations! Published in 2023 at "Cancer Research"
DOI: 10.1158/1538-7445.am2023-5006
Abstract: Abnormal expression and activation of Epidermal Growth Factor Receptor (EGFR) contribute to malignancy development, especially in non-small cell lung cancers (NSCLCs). Although the first- to third-generation EGFR small molecule inhibitors have made significant progress in… read more here.
Keywords: discovery novel; heterobifunctional degraders; egfr mutations; egfr ... See more keywords