Journal ArticleDOI
The new opportunities in medicinal chemistry of fourth-generation EGFR inhibitors to overcome C797S mutation
Reads0
Chats0
TLDR
The recent advances in medicinal chemistry of fourth-generation EGFR-TKIs are discussed, as well as further discussed the clinical challenges and future prospects of treating patients with EGFR mutations resistant to third-generationEGFR- TKIs.About:
This article is published in European Journal of Medicinal Chemistry.The article was published on 2021-01-15. It has received 34 citations till now. The article focuses on the topics: EGFR inhibitors & Epidermal growth factor receptor.read more
Citations
More filters
Journal ArticleDOI
Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors.
TL;DR: The molecular mechanisms underlying resistance to third-generation EGFR inhibitors and the ongoing efforts to address and overcome this chemoresistance are summarized.
Journal ArticleDOI
A sulfonyl fluoride derivative inhibits EGFRL858R/T790M/C797S by covalent modification of the catalytic lysine.
Francesca Ferlenghi,Laura Scalvini,Federica Vacondio,Riccardo Castelli,Nicole Bozza,Giuseppe Marseglia,Silvia Rivara,Alessio Lodola,Silvia La Monica,Roberta Minari,Pier Giorgio Petronini,Roberta Alfieri,Marcello Tiseo,Marco Mor +13 more
TL;DR: UPR1444 (compound 11) is a new sulfonyl fluoride derivative which potently and irreversibly inhibits EGFRL858R/T790M/C797S through the formation of a sulfonamide bond with the catalytic residue Lys745.
Journal ArticleDOI
Conformational Constrained 4-(1-Sulfonyl-3-indol)yl-2-phenylaminopyrimidine Derivatives as New Fourth-Generation Epidermal Growth Factor Receptor Inhibitors Targeting T790M/C797S Mutations.
Hao Chen,Mengzhen Lai,Tao Zhang,Yuqing Chen,Linjiang Tong,Sujie Zhu,Yang Zhou,Xiaomei Ren,Jianping Ding,Hua Xie,Xiaoyun Lu,Ke Ding +11 more
TL;DR: The structure-based design of conformational constrained 4-(1-ethylsufonyl-3-indolyl)-2-phenylaminopyrimidines as new EGFRT790M/C797S inhibitors are reported by using a macrocyclization strategy to combat EGFRC797S-mediated resistance in NSCLC patients.
Journal ArticleDOI
Design, Synthesis, and Biological Evaluation of Novel EGFR PROTACs Targeting Del19/T790M/C797S Mutation.
TL;DR: The design and synthesis of a series of EGFR proteolysis-targeting chimeras (PROTACs) that can rapidly and potently induce EGFR degradation in Ba/F3 cells expressing the EGFRDel19/T790M/C797S mutant are presented.
Journal ArticleDOI
Recent advances in the development of EGFR degraders: PROTACs and LYTACs.
TL;DR: In this paper , the structural properties of EGFR, the inhibitors that have been developed against WT/mutated EGFR and then mainly focuses on the recent advances of EGfr-targeting degraders along with its limitations and unlimited prospects.
References
More filters
Journal ArticleDOI
Discovery of EGF Receptor Inhibitors That Are Selective for the d746‐750/T790M/C797S Mutant through Structure‐Based de Novo Design
TL;DR: A number of nanomolar inhibitors were identified using 2-aryl-4-aminoquinazoline as the molecular core and the modified binding energy function involving a proper dehydration term, which provides important structural insight into the key principles for high inhibitory activities against the d746-750/T790M/C797S mutant.
Journal ArticleDOI
Strategies for monitoring and combating resistance to combination kinase inhibitors for cancer therapy
TL;DR: Recent advances in understanding tumor heterogeneity and resistance to targeted therapies are discussed, focusing on combination kinase inhibitors, and approaches to address these issues in the clinic are discussed.
Journal ArticleDOI
Osimertinib in the treatment of patients with epidermal growth factor receptor T790M mutation-positive metastatic non-small cell lung cancer: clinical trial evidence and experience:
Ivana Sullivan,David Planchard +1 more
TL;DR: Clinical trial development of osimertinib in patients with NSCLC is reviewed, presenting efficacy and safety evidence for its value in the EGFR T790M mutation-positive population and in different settings, including patients with metastatic disease.
Journal ArticleDOI
Kinase Inhibitor Profiling Reveals Unexpected Opportunities to Inhibit Disease-Associated Mutant Kinases
Krisna C. Duong-Ly,Karthik Devarajan,Shuguang Liang,Kurumi Y. Horiuchi,Yuren Wang,Haiching Ma,Jeffrey R. Peterson +6 more
TL;DR: This study conducts a large-scale functional screen of 183 known kinase inhibitors against 76 recombinant mutant kinases and shows how single-dose screening data can provide predictive structure-activity data to guide subsequent inhibitor optimization.
Journal ArticleDOI
4-Oxo-1,4-dihydroquinoline-3-carboxamide Derivatives as New Axl Kinase Inhibitors
Li Tan,Zhang Zhang,Gao Donglin,Jinfeng Luo,Zhengchao Tu,Zhengqiu Li,Lijie Peng,Xiaomei Ren,Xiaomei Ren,Ke Ding,Ke Ding +10 more
TL;DR: 9im tightly bound with Axl protein and potently inhibited its kinase function with a Kd value of 2.7 nM and an IC50 value of 4.0 nM, while was obviously less potent against most of the 403 wild-type kinases evaluated at a relatively high concentration.