EGFR inhibiteurs (EGFR Inhibitors)

Autre Protein Tyrosine Kinase Inhibiteurs

Produits sélectifs disoformes

• Inhibiteurs en vedette
• Inhibiteurs (115)
• Produits chimiques (2)
• Activateur (1)

N° de cat.	Nom du produit	Informations	Citations dutilisation du produit	Validations de produit
S7297	AZD9291 (Osimertinib)	Osimertinib (AZD9291) est un inhibiteur de l'EGFR oral, irréversible et mutant-sélectif avec une IC50 de 12,92, 11,44 et 493,8 nM pour l'EGFR avec délétion de l'exon 19, l'EGFR L858R/T790M et l'EGFR de type sauvage dans les cellules LoVo, respectivement. Phase 3.	Mol Cancer, 2025, 24(1):272 Cancer Discov, 2025, 10.1158/2159-8290.CD-24-1515 Nat Commun, 2025, 16(1):28
S1011	Afatinib (BIBW2992)	Afatinib inhibe l'EGFR/ErbB irréversiblement in vitro avec une IC50 de 0,5, 0,4, 10, 14, 1 nM pour EGFRwt, EGFR L858R , EGFR L858R/T790M ErbB2 (HER2) et ErbB4 (HER4), respectivement. Ce composé induit l'autophagie.	Cell Res, 2025, 10.1038/s41422-025-01110-x Nat Genet, 2025, 10.1038/s41588-025-02158-6 Cell Rep Med, 2025, 6(2):101929
S8724	Lazertinib (YH25448)	Lazertinib (YH25448,GNS-1480) est un EGFR-TKI puissant, hautement sélectif pour les mutants et irréversible, avec des valeurs d'IC50 de 1,7 nM, 2 nM, 5 nM, 20,6 nM et 76 nM pour Del19/T790M, L858R/T790M, Del19, L85R et l'EGFR de type sauvage respectivement, montrant des valeurs d'IC50 beaucoup plus élevées contre ErbB2 et ErbB4.	Cell Rep Med, 2025, 6(2):101929 Cells, 2025, 14(17)1386 Front Oncol, 2025, 15:1533059
S1025	Gefitinib (ZD1839)	Le Gefitinib est un inhibiteur d'EGFR pour Tyr1173, Tyr992, Tyr1173 et Tyr992 dans les cellules NR6wtEGFR et NR6W avec une IC50 de 37 nM, 37 nM, 26 nM et 57 nM, respectivement. Ce composé favorise l'autophagy et l'apoptosis des cellules cancéreuses du poumon via le blocage de la voie PI3K/AKT/mTOR.	Nat Commun, 2025, 16(1):7287 Nat Commun, 2025, 16(1):6451 Cell Rep Med, 2025, 6(2):101929
E4884	Icotinib Hydrochloride	L'Icotinib Hydrochloride (BPI-2009H) est un inhibiteur de la tyrosine kinase du récepteur du facteur de croissance épidermique (EGFR-TKI) très puissant et sélectif, avec une IC50 de 5 nM, utilisé dans le traitement du cancer du poumon non à petites cellules (CPNPC).
S7786	Erlotinib (CP-358774)	Erlotinib est un inhibiteur d'EGFR avec une IC50 de 2 nM, >1000 fois plus sensible pour l'EGFR que le c-Src ou le v-Abl humain. Erlotinib induit l'Autophagy.	Nat Commun, 2025, 16(1):8932 Cell Rep Med, 2025, S2666-3791(25)00272-1 J Exp Clin Cancer Res, 2025, 44(1):290
E5906New	Sunvozertinib	Sunvozertinib (DZD9008) est un inhibiteur oral, puissant et sélectif des ErbBs (EGFR ou Her2), en particulier des formes mutantes des ErbBs. Il inhibe également les insertions EGFR exon 20 NPH insertion, EGFR exon 20 ASV insertion, les mutations EGFR L858R et T790M mutations, Her2 exon 20 YVMA et EGFR WT A431, avec des valeurs de CI50 de 20,4 nM, 20,4 nM, 1,1 nM, 7,5 nM et 80,4 nM, respectivement.	bioRxiv , 2023, 10.1101/2023.07.27.550902
S1023	Erlotinib (CP-358774) Hydrochloride	Erlotinib HCl est un inhibiteur de l'EGFR avec une IC50 de 2 nM dans les tests sans cellules, >1000 fois plus sensible pour l'EGFR que la c-Src humaine ou la v-Abl.	Cell Res, 2025, 10.1038/s41422-025-01110-x Nat Commun, 2025, 16(1):3591 J Exp Clin Cancer Res, 2025, 44(1):68
S2150	Neratinib (HKI-272)	Neratinib est un inhibiteur hautement sélectif de HER2 et d'EGFR avec des IC50 de 59 nM et 92 nM dans les tests sans cellules; il inhibe faiblement KDR et Src, et n'a pas d'inhibition significative sur Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf et c-Met. Phase 3.	Nat Genet, 2025, 57(6):1452-1462 Cancer Discov, 2025, 10.1158/2159-8290.CD-25-0605 J Microbiol, 2025, 63(2):e2409001
S8362	Tucatinib (Irbinitinib, ONT-380, Arry-380)	Tucatinib (Irbinitinib, ONT-380, ARRY-380) est un inhibiteur oral, puissant, sélectif, réversible et compétitif de l'ATP de petite molécule de ErbB-2 (également appelé HER2) avec des IC50 de 8 nM et 7 nM pour ErbB-2 et p95 HER2, respectivement dans des essais basés sur des cellules, montrant une sélectivité d'environ 500 fois pour HER2 par rapport à EGFR. Il a une activité antinéoplasique potentielle.	Cancer Cell, 2025, 43(4):776-796.e14 Cancer Discov, 2025, 10.1158/2159-8290.CD-25-0605 Res Sq, 2025, rs.3.rs-5931887
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Epidermal growth factor receptor (EGFR) was initially discovered in 1962 following the identification of the ligand EGF. Following this, the role of EGFR in protein phosphorylation and tumorigenesis has been established, and the EGF-EGFR signaling axis has consequently been the focus of research in oncology and developmental biology. Situated in the plasma membrane, EGFR has been an attractive target for anticancer therapy as it becomes activated upon ligand binding, recruiting a number of downstream molecules that leads to the activation of major pathways implicated in tumor growth, progression, and survival.^[1][2]

EGFR belongs to the ErbB/HER receptor tyrosine kinase family that encompasses HER2 (ErbB2), HER3 (ErbB3), and HER4 (ErbB4).ii Each constituent of the EGFR family shares a basic domain structure including an N-terminal extracellular domain (subdivided in to domains I through IV), a transmembrane domain, an intracellular kinase domain, and a cytoplasmic C-terminal tail containing several phosphorylation sites that serve as signal transduction modules. The binding of one of several ligands to the extracellular ligand-binding domain induces receptor homo-dimerization or hetero-dimerization and results in kinase activation. Among the EGFR family, it should be noted that ErbB2 is an orphan receptor, characterized by ligand-induced hetero-dimerization with any other family member for activation. Research on ErbB3 initially did not show any intrinsic kinase activity, although recent research findings suggest otherwise.^[3]

In the initial activation response of HER family constituents and similar receptor tyrosine kinases are downregulation events, involving ligand-stimulated endocytosis of occupied receptor accompanied by receptor ubiquitination and followed by lysosomal degradation of both ligands and receptors. Another possibility is that receptor tyrosine kinases are recycled from endosomes to the plasma membrane. Interestingly, HER2 and HER3 are internalized and targeted to lysosomes less efficiently than EGFR, and increased expression of HER2 or HER3 can have a dominant-negative effect on EGFR downregulation and degradation. Whether degradation and/or recycling events occur will affect the number of receptors and thus downstream signalling, profoundly changing the biological response.^[2]

Ligands of EGFR include EGF, transforming growth factor-α, and heparin-binding EGF-like growth factor. Once bound to its ligand, EGFR recruits, phosphorylates and activates all of the following downstream signalling cascades: MAPK, PLC-ϒ/PKC, Ras-Raf-Mek, PI3K-Akt-mTOR/PKB and JAK2-STAT3.^[1][2] EGFR can also mediate cellular processes through the physical interaction with other proteins in the absence of kinase activity or ligand activation.^[1]

Several EGFR-targeting small molecule kinase inhibitors and therapeutic antibodies have been approved by the FDA to treat patients with breast cancer, colorectal cancer, non-small cell lung cancer (NSCLC), head and neck-related squamous cell carcinoma and pancreatic cancer. Despite the role that the EGFR signalling pathway plays in several downstream events that lead to tumorigenesis, currently approved EGFR-targeted therapies show only modest effect on most cancer types.^[1]

Of the classes of compounds that are in clinical trials and/or are approved for clinical practice use, there are two molecular approaches to target EGFR: (1) monoclonal antibodies, directed against the external ligand-binding site of the receptor (i.e. cetuximab and panitumumab), and (2) small molecule tyrosine kinase inhibitors, directed against intracellular tyrosine kinase domain (i.e. gefitinib, erlotinib, and lapatinib). In either case, both classes of compounds target EGFR homodimers and heterodimers. Evidence of this includes the ability of erlotinib to target both EGFR and HER3. Interestingly, the impact of monoclonal antibodies targeting EGFR or HER2 is observed to impact VEGFR expression. EGFR affects VEGFR activity through the MAPK and PI3K signalling pathways and at least three different transcription factors, STAT3, Sp1 and hypoxia-inducible factors (HIFs).ii A close relative of EGFR is EGFRvIII, found to be localized on the cell-surface where it activates several signalling molecules; overexpression of EGFRvIII has been implicated in malignant gliomas. In tumorigenesis, both EGFR and EGFRvIII are observed to be involved in malignant phenotypes in human cancers.^[1]

ErbB proteins are highlighted in oncology research for their ability to drive proliferation, survival, and differentiation. Their overexpression in a variety of human cancers qualifies them as an ideal target for further investigation.^[3]