^
Contact us  to learn more about
our Premium Content:  News alerts, weekly reports and conference planners
BIOMARKER:

EGFR C797S + EGFR T790M + EGFR L858R

i
Other names: EGFR, ERBB, ERBB1, Epidermal growth factor receptor
Entrez ID:
2years
Phase 1 Study of the Efficacy and Safety of Ramucirumab in Combination with Osimertinib in Advanced T790M-Positive EGFR-Mutant Non-Small Cell Lung Cancer. (PubMed, Clin Cancer Res)
Ramucirumab plus osimertinib demonstrated encouraging safety and antitumor activity in T790M-positive EGFR-mutant NSCLC.
Clinical • P1 data • Journal • Combination therapy
|
EGFR (Epidermal growth factor receptor) • KDR (Kinase insert domain receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • MET amplification • EGFR amplification • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • EGFR C797S + EGFR T790M + EGFR exon 19 deletion • EGFR positive • MET amplification + EGFR mutation • EGFR T790M + EGFR C797S • EGFR T790M + exon 19 deletion • EGFR exon 2-7 deletion + EGFR amplification • EGFR mutation + EGFR T790M • EGFR exon 19 deletion + MET amplification • EGFR mutation + EGFR T790M + EGFR C797S
|
Tagrisso (osimertinib)
2years
Design, Synthesis and Biological Evaluation of the Quinazoline Derivatives as L858R/T790M/C797S Triple Mutant Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors. (PubMed, Chem Pharm Bull (Tokyo))
Compound 27 also exhibited good microsomes stabilities in human, rat and mouse liver species, but low bioavailability. This work would be very useful for discovering new quinazoline derivatives as tyrosine kinase inhibitors targeting triple mutant L858R/T790M/C797S.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • EGFR T790M + EGFR C797S • EGFR H1975 • EGFR mutation + EGFR T790M • EGFR mutation + EGFR T790M + EGFR C797S
2years
Structural Basis for EGFR Mutant Inhibition by Trisubstituted Imidazole Inhibitors. (PubMed, J Med Chem)
Selective N-methylation of the H-bond accepting nitrogen ablates inhibitor potency, confirming the role of the K745 H-bond in potent, non-covalent inhibition of C797S variant. Insights from these studies offer new strategies for developing next generation inhibitors targeting EGFR in non-small cell lung cancer.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • EGFR T790M + EGFR C797S • EGFR mutation + EGFR T790M • EGFR mutation + EGFR T790M + EGFR C797S
2years
CH7233163 overcomes osimertinib resistant EGFR-Del19/T790M/C797S mutation. (PubMed, Mol Cancer Ther)
Furthermore, crystal structure analysis suggested that CH7233163 is a non-covalent ATP competitive inhibitor for EGFR-Del19/T790M/C797S that utilizes multiple interactions with the EGFR's αC-helix-in conformation to achieve potent inhibitory activity and mutant selectivity. Therefore, we conclude that CH7233163 is a potentially effective therapy for osimertinib resistant patients, especially in cases of EGFR-Del19/T790M/C797S.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • EGFR T790M + EGFR C797S • EGFR mutation + EGFR T790M • EGFR mutation + EGFR T790M + EGFR C797S
|
Tagrisso (osimertinib) • CH7233163
over2years
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. (PubMed, J Cell Biochem)
According to our computational simulation, the results supported the experimental models and, therefore, could confirm and predict the molecular mechanism of drug efficacy.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • EGFR L718Q • EGFR mutation + EGFR T790M • EGFR mutation + EGFR T790M + EGFR C797S
|
Tagrisso (osimertinib)
over2years
EGFR mutation genotypes affect efficacy and resistance mechanisms of osimertinib in T790M-positive NSCLC patients. (PubMed, Transl Lung Cancer Res)
Our findings indicate that the EGFR 19Del subtypes affect the clinical outcomes and resistance mechanisms to osimertinib in T790M-positive patients. Identifying patients with relatively worse treatment outcomes may be informative for establishing new therapies for these patients.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • EGFR C797S + EGFR T790M + EGFR exon 19 deletion • EGFR T790M + exon 19 deletion • EGFR L858R + EGFR exon 19 deletion
|
Tagrisso (osimertinib)
over2years
Start selective and rigidify: The discovery path towards a next generation of EGFR tyrosine kinase inhibitors. (PubMed, J Med Chem)
BI-4020 potently inhibits the above described EGFR variants and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the molecule through macrocyclization.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R
over2years
Design, synthesis and biological evaluation of potent EGFR kinase inhibitors against 19D/T790M/C797S mutation. (PubMed, Bioorg Med Chem Lett)
EGFR mutation is one of the primary reasons for the emergence of resistance after treatment with the third-generation EGFR inhibitors such as AZD9291, CO1686 and Olmutinib. Furthermore, 12e exhibited good growth inhibition activity, induced G1 phase cell cycle arrest and apoptosis in BaF3/EGFR cells by suppressing EGFR phosphorylation signaling pathway. In all, our study might provide a novel structural design method and lay the solid foundation for the development of the 4th generation EGFR inhibitors.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R
|
Tagrisso (osimertinib) • Xegafri (rociletinib) • Olita (olmutinib)
over2years
Design, synthesis and biological evaluation of 4-aniline quinazoline derivatives conjugated with hydrogen sulfide (HS) donors as potent EGFR inhibitors against L858R resistance mutation. (PubMed, Eur J Med Chem)
In addition, compound 9h exhibits weak anti-proliferative effects on other tumor cells (HepG2, MCF-7, HT-29 and A431) and has lower toxic effect on HUVEC cells than AZD9291 (positive control)...Cell cycle analysis reveals that compound 9h suppresses the proliferation of cells by inducing cell cycle arrest in G0-G1 phase. The result of HS release evaluation suggests that the HS release of compound 9h is significantly more and faster than other compounds.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R
|
Tagrisso (osimertinib)
over2years
Mechanistic Study of Potent Fluorinated EGFR Kinase Inhibitors with a Quinazoline Scaffold against L858R/T790M/C797S Resistance Mutation: Unveiling the Fluorine Substituent Cooperativity Effect on the Inhibitory Activity. (PubMed, J Phys Chem B)
Per-residue energy-based hierarchical clustering analysis suggests that three hot-spot residues, L718, K745, and D855, are the key in achieving optimal binding modes for 25g with higher affinity in the EGFR compared to 25a. This study provides a rationale for the superior EGFR-inhibitory potency exhibited by 25g over 25a, which is expected to be useful for the future rational structure-based design of novel EGFR inhibitors with improved potency and selectivity.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R
over2years
[VIRTUAL] JNJ-61186372, a novel EGFR/c-Met bispecific antibody, exhibits potent antitumor activity in broad-spectrum of acquired resistance to EGFR-TKIs (AACR-II 2020)
Background: 1st generation (erlotinib & gefitinib), 2nd generation (afatinib), and 3rd generation (osimertinib) EGFR TKIs have marked efficacy in patient with EGFR-mutant NSCLC. Our results suggest that JNJ-372 will provide potential and effective therapeutic options for patients with no therapeutic option to overcome broad-spectrum of acquired resistance to EGFR-TKIs.
Preclinical
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
KRAS mutation • EGFR mutation • EGFR L858R • MET amplification • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • MET expression
|
Tagrisso (osimertinib) • erlotinib • Gilotrif (afatinib) • gefitinib • Rybrevant (amivantamab-vmjw)
over2years
[VIRTUAL] BRAF fusion in lung cancer. (ASCO 2020)
BRAF fusion had low frequency in lung cancer and occurred at different stage during disease development. BRAF inhibitors maybe a potential strategy for BRAF fusion lung cancers. As TKIs resistance mechanism, BRAF fusion is a huge clinical challenge, indicate the importance of further research.
Tumor Mutational Burden
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden)
|
BRAF V600E • KRAS mutation • EGFR mutation • TMB-H • BRAF V600 • EGFR L858R • EGFR C797S • TMB-L • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R • BRAF fusion • EGFR T790M + KRAS mutation
over2years
[VIRTUAL] Concurrent osimertinib plus gefitinib for first-line treatment of EGFR-mutated non-small cell lung cancer (NSCLC). (ASCO 2020)
Combination therapy with osimertinib and gefitinib is tolerable for first-line treatment of EGFR-mutated NSCLC and resulted in rapid plasma clearance of the EGFR mutation. The observed ORR is consistent with previously reported first-line response rates to osimertinib. Analysis of survival outcomes and acquired resistance mechanisms are pending data maturity and will facilitate understanding of the role of first-line dual EGFR TKI therapy for this pt population.
Clinical
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR L858R + EGFR T790M • EGFR C797S + EGFR T790M + EGFR L858R
|
Tagrisso (osimertinib) • gefitinib