Targeting EGFRL858R/T790M and EGFRL858R/T790M/C797S resistance mutations in NSCLC: Current developments in medicinal chemistry

A structure-guided optimization of pyrido[2,3- d ]pyrimidin-7-ones as selective inhibitors of EGFR L858R/T790M mutant with improved pharmacokinetic properties

(2017) Lei Yu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Recent updates on third generation EGFR inhibitors and emergence of fourth generation EGFR inhibitors to combat C797S resistance

(2017) Harun Patel et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Trisubstituted Imidazoles with a Rigidized Hinge Binding Motif Act As Single Digit nM Inhibitors of Clinically Relevant EGFR L858R/T790M and L858R/T790M/C797S Mutants: An Example of Target Hopping

(2017) Michael Juchum et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Guided Development of Covalent and Mutant-Selective Pyrazolopyrimidines to Target T790M Drug Resistance in Epidermal Growth Factor Receptor

(2017) Julian Engel et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of N-((3R,4R)-4-Fluoro-1-(6-((3-methoxy-1-methyl-1H-pyrazol-4-yl)amino)-9-methyl-9H-purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR

(2017) Simon Planken et al.   JOURNAL OF MEDICINAL CHEMISTRY

Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site

(2017) Marcel Günther et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of an UPLC–MS/MS method for quantification of Avitinib (AC0010) and its five metabolites in human cerebrospinal fluid: Application to a study of the blood-brain barrier penetration rate of non-small cell lung cancer patients

(2017) Weicong Wang et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

An LC–MS/MS method for quantification of AC0010, a novel mutant-selective epidermal growth factor receptor (EGFR) inhibitor, and its metabolites in human plasma and the application to a pharmacokinetic study

(2017) Lu Wang et al.   JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer

(2017) Tony S. Mok et al.   NEW ENGLAND JOURNAL OF MEDICINE

Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine Kinase EGFR

(2016) Julian Engel et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Lung Cancer: EGFR Inhibitors with Low Nanomolar Activity against a Therapy-Resistant L858R/T790M/C797S Mutant

(2016) Marcel Günther et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Recent progress on third generation covalent EGFR inhibitors

(2016) Hengmiao Cheng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Cancer statistics, 2016

(2016) Rebecca L. Siegel et al.   CA-A CANCER JOURNAL FOR CLINICIANS

EGF816 Exerts Anticancer Effects in Non–Small Cell Lung Cancer by Irreversibly and Selectively Targeting Primary and Acquired Activating Mutations in the EGF Receptor

(2016) Yong Jia et al.   CANCER RESEARCH

Osimertinib: First Global Approval

(2016) Sarah L. Greig   DRUGS

Olmutinib: First Global Approval

(2016) Esther S. Kim   DRUGS

Rociletinib, a third generation EGFR tyrosine kinase inhibitor: current data and future directions

(2016) Jody C. Chuang et al.   EXPERT OPINION ON PHARMACOTHERAPY

Challenges and Perspectives on the Development of Small-Molecule EGFR Inhibitors against T790M-Mediated Resistance in Non-Small-Cell Lung Cancer

(2016) Zhendong Song et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a Noncovalent, Mutant-Selective Epidermal Growth Factor Receptor Inhibitor

(2016) Bryan K. Chan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Tyrosine Kinase Inhibitors. 20. Optimization of Substituted Quinazoline and Pyrido[3,4-d]pyrimidine Derivatives as Orally Active, Irreversible Inhibitors of the Epidermal Growth Factor Receptor Family

(2016) Jeff B. Smaill et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants

(2016) Hengmiao Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers

(2016) Gérald Lelais et al.   JOURNAL OF MEDICINAL CHEMISTRY

1300: Efficacy and safety of BI 1482694 (HM61713), an EGFR mutant-specific inhibitor, in T790M-positive NSCLC at the recommended phase II dose

(2016) K. Park et al.   Journal of Thoracic Oncology

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study

(2016) Glenwood Goss et al.   LANCET ONCOLOGY

AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients

(2016) X. Xu et al.   MOLECULAR CANCER THERAPEUTICS

Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors

(2016) Yong Jia et al.   NATURE

Allosteric EGFR Inhibitors Overcome Resistance Mutations

(2016)   Cancer Discovery

EGFR-independent mechanisms of acquired resistance to AZD9291 in EGFR T790M-positive NSCLC patients

(2015) D. Planchard et al.   ANNALS OF ONCOLOGY

Global cancer statistics, 2012

(2015) Lindsey A. Torre et al.   CA-A CANCER JOURNAL FOR CLINICIANS

Abstract 2586: ASP8273 selectively inhibits mutant EGFR signal pathway and induces tumor shrinkage in EGFR mutated tumor models

(2015) Satoshi Konagai et al.   CANCER RESEARCH

EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors

(2015) D. Ercan et al.   CLINICAL CANCER RESEARCH

Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study

(2015) Robert Heald et al.   JOURNAL OF MEDICINAL CHEMISTRY

Acquired EGFR C797S mutation mediates resistance to AZD9291 in non–small cell lung cancer harboring EGFR T790M

(2015) Kenneth S Thress et al.   NATURE MEDICINE

AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer

(2015) Pasi A. Jänne et al.   NEW ENGLAND JOURNAL OF MEDICINE

C5-substituted pyrido[2,3-d]pyrimidin-7-ones as highly specific kinase inhibitors targeting the clinical resistance-related EGFRT790M mutant

(2015) Tianfeng Xu et al.   MedChemComm

Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR

(2015) Marian C. Bryan et al.   ACS Medicinal Chemistry Letters

Heterogeneity Underlies the Emergence of EGFRT790 Wild-Type Clones Following Treatment of T790M-Positive Cancers with a Third-Generation EGFR Inhibitor

(2015) Z. Piotrowska et al.   Cancer Discovery

Dacomitinib in lung cancer: a “lost generation” EGFR tyrosine-kinase inhibitor from a bygone era?

(2015) Sai-Hong Ou et al.   Drug Design Development and Therapy

Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application

(2015) Paolo Maione et al.   Therapeutic Advances in Medical Oncology

Abstract 1728: ASP8273, a novel mutant-selective irreversible EGFR inhibitor, inhibits growth of non-small cell lung cancer (NSCLC) cells with EGFR activating and T790M resistance mutations

(2015) Hideki Sakagami et al.   CANCER RESEARCH

Poor response to erlotinib in patients with tumors containing baseline EGFR T790M mutations found by routine clinical molecular testing

(2014) H. A. Yu et al.   ANNALS OF ONCOLOGY

Discovery of a Potent and Selective EGFR Inhibitor (AZD9291) of Both Sensitizing and T790M Resistance Mutations That Spares the Wild Type Form of the Receptor

(2014) M. Raymond V. Finlay et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Selective and Noncovalent Diaminopyrimidine-Based Inhibitors of Epidermal Growth Factor Receptor Containing the T790M Resistance Mutation

(2014) Emily J. Hanan et al.   JOURNAL OF MEDICINAL CHEMISTRY

AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer

(2014) D. A. E. Cross et al.   Cancer Discovery

Pyrimido[4,5-d]pyrimidin-4(1H)-one Derivatives as Selective Inhibitors of EGFR Threonine790to Methionine790(T790M) Mutants

(2013) Tianfeng Xu et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Structure- and Reactivity-Based Development of Covalent Inhibitors of the Activating and Gatekeeper Mutant Forms of the Epidermal Growth Factor Receptor (EGFR)

(2013) Richard A. Ward et al.   JOURNAL OF MEDICINAL CHEMISTRY

Afatinib—new therapy option for EGFR-mutant lung cancer

(2013) Helena A. Yu et al.   Nature Reviews Clinical Oncology

Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

(2013) A. O. Walter et al.   Cancer Discovery

Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): A better mousetrap? A review of the clinical evidence

(2012) Sai-Hong Ignatius Ou   CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial

(2012) Rafael Rosell et al.   LANCET ONCOLOGY

Molecular pathology of lung cancer: key to personalized medicine

(2012) Liang Cheng et al.   MODERN PATHOLOGY

Structure-Based Approach for the Discovery of Pyrrolo[3,2-d]pyrimidine-Based EGFR T790M/L858R Mutant Inhibitors

(2012) Satoshi Sogabe et al.   ACS Medicinal Chemistry Letters

Noncovalent Wild-type–Sparing Inhibitors of EGFR T790M

(2012) Ho-June Lee et al.   Cancer Discovery

New Strategies in Overcoming Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Cancer

(2011) G. R. Oxnard et al.   CLINICAL CANCER RESEARCH

Rebiopsy of Lung Cancer Patients with Acquired Resistance to EGFR Inhibitors and Enhanced Detection of the T790M Mutation Using a Locked Nucleic Acid-Based Assay

(2011) M. E. Arcila et al.   CLINICAL CANCER RESEARCH

Epithelial to Mesenchymal Transition in an Epidermal Growth Factor Receptor-Mutant Lung Cancer Cell Line with Acquired Resistance to Erlotinib

(2011) Kenichi Suda et al.   Journal of Thoracic Oncology

Small-cell lung cancer

(2011) Jan P van Meerbeeck et al.   LANCET

Conversion from the “oncogene addiction” to “drug addiction” by intensive inhibition of the EGFR and MET in lung cancer with activating EGFR mutation

(2011) Kenichi Suda et al.   LUNG CANCER

FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR

(2011) Trever G. Bivona et al.   NATURE

Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors

(2011) L. V. Sequist et al.   Science Translational Medicine

Loss of PTEN Expression by Blocking Nuclear Translocation of EGR1 in Gefitinib-Resistant Lung Cancer Cells Harboring Epidermal Growth Factor Receptor-Activating Mutations

(2010) C. Yamamoto et al.   CANCER RESEARCH

Chemogenomic Profiling Provides Insights into the Limited Activity of Irreversible EGFR Inhibitors in Tumor Cells Expressing the T790M EGFR Resistance Mutation

(2010) M. L. Sos et al.   CANCER RESEARCH

Acquired Resistance to EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Lung Cancer: Distinct Natural History of Patients with Tumors Harboring the T790M Mutation

(2010) Geoffrey R. Oxnard et al.   CLINICAL CANCER RESEARCH

Neratinib, an Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor: Results of a Phase II Trial in Patients With Advanced Non–Small-Cell Lung Cancer

(2010) Lecia V. Sequist et al.   JOURNAL OF CLINICAL ONCOLOGY

Clinical and molecular evidences of epithelial to mesenchymal transition in acquired resistance to EGFR-TKIs

(2010) Jin-Haeng Chung et al.   LUNG CANCER

Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR

(2010) Makoto Maemondo et al.   NEW ENGLAND JOURNAL OF MEDICINE

Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Who Harbor EML4-ALK

(2009) Alice T. Shaw et al.   JOURNAL OF CLINICAL ONCOLOGY

Novel mutant-selective EGFR kinase inhibitors against EGFR T790M

(2009) Wenjun Zhou et al.   NATURE

Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors

(2009) T John et al.   ONCOGENE

Better survival with EGFR exon 19 than exon 21 mutations in gefitinib-treated non-small cell lung cancer patients is due to differential inhibition of downstream signals

(2008) Jian-quan Zhu et al.   CANCER LETTERS

Hepatocyte Growth Factor Induces Gefitinib Resistance of Lung Adenocarcinoma with Epidermal Growth Factor Receptor-Activating Mutations

(2008) S. Yano et al.   CANCER RESEARCH

Acquired Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors Associated with a Novel T854A Mutation in a Patient with EGFR-Mutant Lung Adenocarcinoma

(2008) J. Bean et al.   CLINICAL CANCER RESEARCH

Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer

(2008) Helena Linardou et al.   LANCET ONCOLOGY

Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor

(2008) A. J. Gonzales et al.   MOLECULAR CANCER THERAPEUTICS

BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

(2008) D Li et al.   ONCOGENE

The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP

(2008) C.-H. Yun et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA