Research graph
References from Discovery of Potent and Selective VHL-Recruiting PROTAC Degraders Targeting EGFR with Improved Developability and Potent Anti-NSCLC Efficacy. Local targets link to admitted publications; unresolved targets remain external evidence.
Cancer statistics
10.3322/caac.21871 · 2025 · External reference
Epidermal growth factor receptor mutations in lung cancer
10.1038/nrc2088 · 2007 · External reference
Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor-mutant non-small cell lung cancer
10.1016/j.lungcan.2016.01.003 · 2016 · External reference
Challenges and perspectives on the development of small-molecule EGFR inhibitors against T790M-mediated resistance in non-small-cell lung cancer
10.1021/acs.jmedchem.5b00840 · 2016 · External reference
Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC - mechanisms and evolving treatment approaches
10.1038/s41571-025-01085-z · 2026 · External reference
Understanding and targeting resistance mechanisms in NSCLC
10.1038/nrc.2017.84 · 2017 · External reference
Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer
10.1186/s12943-018-0777-1 · 2018 · External reference
Overcoming therapy resistance in EGFR-mutant lung cancer
10.1038/s43018-021-00195-8 · 2021 · External reference
Recent progress of small-molecule epidermal growth factor receptor (EGFR) inhibitors against C797S resistance in non-small-cell lung cancer
10.1021/acs.jmedchem.7b01310 · 2018 · External reference
Novel third-generation EGFR tyrosine kinase inhibitors and strategies to overcome therapeutic resistance in lung cancer
10.1158/0008-5472.can-18-1281 · 2019 · External reference
Emerging approaches to overcome acquired drug resistance obstacles to osimertinib in non-small-cell lung cancer
10.1021/acs.jmedchem.1c00876 · 2022 · External reference
PROTAC targeted protein degraders: the past is prologue
10.1038/s41573-021-00371-6 · 2022 · External reference
Targeted protein degradation for cancer therapy
10.1038/s41568-025-00817-8 · 2025 · External reference
The advantages of targeted protein degradation over inhibition: An RTK case study
10.1016/j.chembiol.2017.09.009 · 2018 · External reference
Discovery of potent and selective epidermal growth factor receptor (EGFR) bifunctional small-molecule degraders
10.1021/acs.jmedchem.9b01566 · 2020 · External reference
Exploring degradation of mutant and wild-type epidermal growth factor receptors induced by proteolysis-targeting chimeras
10.1021/acs.jmedchem.2c00345 · 2022 · External reference
Effective degradation of EGFR(L858R+T790M) mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems
10.1016/j.ejmech.2021.113328 · 2021 · External reference
Design and synthesis of selective degraders of EGFRL858R/T790M mutant
10.1016/j.ejmech.2020.112199 · 2020 · External reference
Discovery and biological evaluation of proteolysis targeting chimeras (PROTACs) as an EGFR degraders based on osimertinib and lenalidomide
10.1016/j.bmcl.2020.127167 · 2020 · External reference
Design and synthesis of proteolysis targeting chimeras (PROTACs) as an EGFR degrader based on CO-1686
10.1016/j.ejmech.2022.114455 · 2022 · External reference
Discovery of potent PROTACs targeting EGFR mutants through the optimization of covalent EGFR ligands
10.1021/acs.jmedchem.1c01827 · 2022 · External reference
Discovery of highly potent and selective CRBN-recruiting EGFRL858R/T790M degraders in vivo
10.1016/j.ejmech.2022.114509 · 2022 · External reference
Discovery of potent small molecule PROTACs targeting mutant EGFR
10.1016/j.ejmech.2020.112781 · 2020 · External reference
Design, synthesis, and biological evaluation of novel EGFR PROTACs targeting Del19/T790M/C797S mutation
10.1021/acsmedchemlett.1c00645 · 2022 · External reference
HJM-561, a potent, selective, and orally bioavailable EGFR PROTAC that overcomes osimertinib-resistant EGFR triple mutations
10.1158/1535-7163.mct-21-0835 · 2022 · External reference
Design, synthesis, and biological evaluation of novel EGFR PROTACs targeting C797S mutation
10.1021/acs.jmedchem.4c00107 · 2024 · External reference
Discovery of a novel EGFR PROTAC degrader against C797S resistance mutation with potent antitumor efficacy in NSCLC treatment
10.1021/acs.jmedchem.5c00693 · 2025 · External reference
Mutant-selective allosteric EGFR degraders are effective against a broad range of drug-resistant mutations
10.1002/anie.202003500 · 2020 · External reference
Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers
10.1016/j.lungcan.2015.01.020 · 2015 · External reference
EGFR mutation and brain metastasis in pulmonary adenocarcinomas
10.1097/jto.0000000000000069 · 2014 · External reference
Discovery and evaluation of clinical candidate AZD3759, a potent, oral active, central nervous system-penetrant, epidermal growth factor receptor tyrosine kinase inhibitor
10.1021/acs.jmedchem.5b01073 · 2015 · External reference
Insights into the aberrant activity of mutant EGFR kinase domain and drug recognition
10.1016/j.str.2012.11.014 · 2013 · External reference
A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo
10.1038/s41467-022-33430-6 · 2022 · External reference
A novel small-molecule PROTAC selectively promotes tau clearance to improve cognitive functions in Alzheimer-like models
10.7150/thno.55680 · 2021 · External reference
BBB-Permeable PROTACs: Where Do We Stand?
10.1021/acsmedchemlett.5c00768 · 2026 · External reference
Beyond rule of five and PROTACs in modern drug discovery: Polarity reducers, chameleonicity, and the evolving physicochemical landscape
10.1021/acs.jmedchem.3c02332 · 2024 · External reference
Impact of linker composition on VHL PROTAC cell permeability
10.1021/acs.jmedchem.4c02492 · 2025 · External reference
Solution conformations shed light on PROTAC cell permeability
10.1021/acsmedchemlett.0c00556 · 2021 · External reference
Discovery of XL01126: A potent, fast, cooperative, selective, orally bioavailable, and blood-brain barrier penetrant PROTAC degrader of leucine-rich tepeat kinase 2
10.1021/jacs.2c05499 · 2022 · External reference
Linker methylation as a strategy to enhance PROTAC oral bioavailability: Insights from molecular properties and conformational analysis
10.1021/acs.jmedchem.5c01497 · 2025 · External reference
Strategies toward discovery of potent and orally bioavailable proteolysis targeting chimera degraders of androgen receptor for the treatment of prostate cancer
10.1021/acs.jmedchem.1c00882 · 2021 · External reference
Discovery of a novel potent and orally efficacious PROTAC degrader of HPK1 for tumor immunotherapy
10.1021/acs.jmedchem.5c00970 · 2025 · External reference
Strategies for the discovery of oral PROTAC degraders aimed at cancer therapy
10.1016/j.xcrp.2022.101062 · 2022 · External reference
Lessons learned in linking PROTACs from discovery to the clinic
10.1038/s41570-025-00784-6 · 2025 · External reference
Discovery of ARD-69 as a highly potent proteolysis targeting chimera (PROTAC) degrader of androgen receptor (AR) for the treatment of prostate cancer
10.1021/acs.jmedchem.8b01631 · 2019 · External reference
Unresolved reference
External reference
Discovery of KRAS(G12D) selective degrader ASP3082
10.1038/s42004-025-01662-4 · 2025 · External reference
Unresolved reference
External reference
Lessons in PROTAC design from selective degradation with a promiscuous warhead
10.1016/j.chembiol.2017.09.010 · 2018 · External reference
Affinity and cooperativity modulate ternary complex formation to drive targeted protein degradation
10.1038/s41467-023-39904-5 · 2023 · External reference
Unhooking the hook: Optimization of the Aurora A targeting PROTAC JB170 to CCT400028, an in vitro degrader chemical probe
10.1021/acs.jmedchem.5c03024 · 2026 · External reference
Physicochemical property determinants of oral absorption for PROTAC protein degraders
10.1021/acs.jmedchem.3c00740 · 2023 · External reference
Structural and physicochemical features of oral PROTACs
10.1021/acs.jmedchem.4c01017 · 2024 · External reference
Demystifying brain penetration in central nervous system drug discovery. Miniperspective
10.1021/jm301297f · 2013 · External reference
Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties
10.1021/cn100008c · 2010 · External reference
PROTACs targeting BRM (SMARCA2) afford selective in vivo degradation over BRG1 (SMARCA4) and are active in BRG1 mutant xenograft tumor models
10.1021/acs.jmedchem.3c01781 · 2024 · External reference
Unresolved reference
External reference
Unresolved reference
External reference
Mutant-selective allosteric EGFR degraders are effective against a broad range of drug-resistant mutations
10.1002/anie.202003500 · ExternalCitation · doi-reference
Discovery and biological evaluation of proteolysis targeting chimeras (PROTACs) as an EGFR degraders based on osimertinib and lenalidomide
10.1016/j.bmcl.2020.127167 · ExternalCitation · doi-reference
The advantages of targeted protein degradation over inhibition: An RTK case study
10.1016/j.chembiol.2017.09.009 · ExternalCitation · doi-reference
Lessons in PROTAC design from selective degradation with a promiscuous warhead
10.1016/j.chembiol.2017.09.010 · ExternalCitation · doi-reference
Design and synthesis of selective degraders of EGFRL858R/T790M mutant
10.1016/j.ejmech.2020.112199 · ExternalCitation · doi-reference
Discovery of potent small molecule PROTACs targeting mutant EGFR
10.1016/j.ejmech.2020.112781 · ExternalCitation · doi-reference
Effective degradation of EGFR(L858R+T790M) mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems
10.1016/j.ejmech.2021.113328 · ExternalCitation · doi-reference
Design and synthesis of proteolysis targeting chimeras (PROTACs) as an EGFR degrader based on CO-1686
10.1016/j.ejmech.2022.114455 · ExternalCitation · doi-reference
Discovery of highly potent and selective CRBN-recruiting EGFRL858R/T790M degraders in vivo
10.1016/j.ejmech.2022.114509 · ExternalCitation · doi-reference
Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers
10.1016/j.lungcan.2015.01.020 · ExternalCitation · doi-reference
Next-generation epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor-mutant non-small cell lung cancer
10.1016/j.lungcan.2016.01.003 · ExternalCitation · doi-reference
Insights into the aberrant activity of mutant EGFR kinase domain and drug recognition
10.1016/j.str.2012.11.014 · ExternalCitation · doi-reference
Strategies for the discovery of oral PROTAC degraders aimed at cancer therapy
10.1016/j.xcrp.2022.101062 · ExternalCitation · doi-reference
Emerging approaches to overcome acquired drug resistance obstacles to osimertinib in non-small-cell lung cancer
10.1021/acs.jmedchem.1c00876 · ExternalCitation · doi-reference
Strategies toward discovery of potent and orally bioavailable proteolysis targeting chimera degraders of androgen receptor for the treatment of prostate cancer
10.1021/acs.jmedchem.1c00882 · ExternalCitation · doi-reference
Discovery of potent PROTACs targeting EGFR mutants through the optimization of covalent EGFR ligands
10.1021/acs.jmedchem.1c01827 · ExternalCitation · doi-reference
Exploring degradation of mutant and wild-type epidermal growth factor receptors induced by proteolysis-targeting chimeras
10.1021/acs.jmedchem.2c00345 · ExternalCitation · doi-reference
Physicochemical property determinants of oral absorption for PROTAC protein degraders
10.1021/acs.jmedchem.3c00740 · ExternalCitation · doi-reference
PROTACs targeting BRM (SMARCA2) afford selective in vivo degradation over BRG1 (SMARCA4) and are active in BRG1 mutant xenograft tumor models
10.1021/acs.jmedchem.3c01781 · ExternalCitation · doi-reference
Beyond rule of five and PROTACs in modern drug discovery: Polarity reducers, chameleonicity, and the evolving physicochemical landscape
10.1021/acs.jmedchem.3c02332 · ExternalCitation · doi-reference
Design, synthesis, and biological evaluation of novel EGFR PROTACs targeting C797S mutation
10.1021/acs.jmedchem.4c00107 · ExternalCitation · doi-reference
Structural and physicochemical features of oral PROTACs
10.1021/acs.jmedchem.4c01017 · ExternalCitation · doi-reference
Impact of linker composition on VHL PROTAC cell permeability
10.1021/acs.jmedchem.4c02492 · ExternalCitation · doi-reference
Challenges and perspectives on the development of small-molecule EGFR inhibitors against T790M-mediated resistance in non-small-cell lung cancer
10.1021/acs.jmedchem.5b00840 · ExternalCitation · doi-reference
Discovery and evaluation of clinical candidate AZD3759, a potent, oral active, central nervous system-penetrant, epidermal growth factor receptor tyrosine kinase inhibitor
10.1021/acs.jmedchem.5b01073 · ExternalCitation · doi-reference
Discovery of a novel EGFR PROTAC degrader against C797S resistance mutation with potent antitumor efficacy in NSCLC treatment
10.1021/acs.jmedchem.5c00693 · ExternalCitation · doi-reference
Discovery of a novel potent and orally efficacious PROTAC degrader of HPK1 for tumor immunotherapy
10.1021/acs.jmedchem.5c00970 · ExternalCitation · doi-reference
Linker methylation as a strategy to enhance PROTAC oral bioavailability: Insights from molecular properties and conformational analysis
10.1021/acs.jmedchem.5c01497 · ExternalCitation · doi-reference
Unhooking the hook: Optimization of the Aurora A targeting PROTAC JB170 to CCT400028, an in vitro degrader chemical probe
10.1021/acs.jmedchem.5c03024 · ExternalCitation · doi-reference
Recent progress of small-molecule epidermal growth factor receptor (EGFR) inhibitors against C797S resistance in non-small-cell lung cancer
10.1021/acs.jmedchem.7b01310 · ExternalCitation · doi-reference
Discovery of ARD-69 as a highly potent proteolysis targeting chimera (PROTAC) degrader of androgen receptor (AR) for the treatment of prostate cancer
10.1021/acs.jmedchem.8b01631 · ExternalCitation · doi-reference
Discovery of potent and selective epidermal growth factor receptor (EGFR) bifunctional small-molecule degraders
10.1021/acs.jmedchem.9b01566 · ExternalCitation · doi-reference
Solution conformations shed light on PROTAC cell permeability
10.1021/acsmedchemlett.0c00556 · ExternalCitation · doi-reference
Design, synthesis, and biological evaluation of novel EGFR PROTACs targeting Del19/T790M/C797S mutation
10.1021/acsmedchemlett.1c00645 · ExternalCitation · doi-reference
BBB-Permeable PROTACs: Where Do We Stand?
10.1021/acsmedchemlett.5c00768 · ExternalCitation · doi-reference
Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties
10.1021/cn100008c · ExternalCitation · doi-reference
Discovery of XL01126: A potent, fast, cooperative, selective, orally bioavailable, and blood-brain barrier penetrant PROTAC degrader of leucine-rich tepeat kinase 2
10.1021/jacs.2c05499 · ExternalCitation · doi-reference
Demystifying brain penetration in central nervous system drug discovery. Miniperspective
10.1021/jm301297f · ExternalCitation · doi-reference
Understanding and targeting resistance mechanisms in NSCLC
10.1038/nrc.2017.84 · ExternalCitation · doi-reference
Epidermal growth factor receptor mutations in lung cancer
10.1038/nrc2088 · ExternalCitation · doi-reference
A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo
10.1038/s41467-022-33430-6 · ExternalCitation · doi-reference
Affinity and cooperativity modulate ternary complex formation to drive targeted protein degradation
10.1038/s41467-023-39904-5 · ExternalCitation · doi-reference
Targeted protein degradation for cancer therapy
10.1038/s41568-025-00817-8 · ExternalCitation · doi-reference
Lessons learned in linking PROTACs from discovery to the clinic
10.1038/s41570-025-00784-6 · ExternalCitation · doi-reference
Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC - mechanisms and evolving treatment approaches
10.1038/s41571-025-01085-z · ExternalCitation · doi-reference
PROTAC targeted protein degraders: the past is prologue
10.1038/s41573-021-00371-6 · ExternalCitation · doi-reference
Discovery of KRAS(G12D) selective degrader ASP3082
10.1038/s42004-025-01662-4 · ExternalCitation · doi-reference
Overcoming therapy resistance in EGFR-mutant lung cancer
10.1038/s43018-021-00195-8 · ExternalCitation · doi-reference
EGFR mutation and brain metastasis in pulmonary adenocarcinomas
10.1097/jto.0000000000000069 · ExternalCitation · doi-reference
Novel third-generation EGFR tyrosine kinase inhibitors and strategies to overcome therapeutic resistance in lung cancer
10.1158/0008-5472.can-18-1281 · ExternalCitation · doi-reference
HJM-561, a potent, selective, and orally bioavailable EGFR PROTAC that overcomes osimertinib-resistant EGFR triple mutations
10.1158/1535-7163.mct-21-0835 · ExternalCitation · doi-reference
Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer
10.1186/s12943-018-0777-1 · ExternalCitation · doi-reference
Cancer statistics
10.3322/caac.21871 · ExternalCitation · doi-reference
A novel small-molecule PROTAC selectively promotes tau clearance to improve cognitive functions in Alzheimer-like models
10.7150/thno.55680 · ExternalCitation · doi-reference
