EGFR Inhibitoren (EGFR Inhibitors)

Weitere Protein Tyrosine Kinase Inhibitoren

Isoformspezifische Produkte

• Ausgewählte Inhibitoren
• Inhibitoren (115)
• Chemikalien (2)
• Aktivator (1)

Kat.-Nr.	Produktname	Informationen	Publikationen	Validierung
S7297	AZD9291 (Osimertinib)	Osimertinib (AZD9291) ist ein oraler, irreversibler und mutantenselektiver EGFR-Inhibitor mit einer IC50 von 12,92, 11,44 und 493,8 nM für Exon 19-Deletion EGFR, L858R/T790M EGFR bzw. WT EGFR in LoVo-Zellen. 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 hemmt EGFR/ErbB irreversibel in vitro mit einer IC50 von 0,5, 0,4, 10, 14, 1 nM für EGFRwt, EGFR L858R , EGFR L858R/T790M ErbB2 (HER2) bzw. ErbB4 (HER4). Diese Verbindung induziert Autophagy.	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) ist ein potenter, hochmutantenselektiver und irreversibler EGFR-TKI mit IC50-Werten von 1,7 nM, 2 nM, 5 nM, 20,6 nM und 76 nM für Del19/T790M, L858R/T790M, Del19, L85R bzw. Wildtyp EGFR, der viel höhere IC50-Werte gegen ErbB2 und ErbB4 aufweist.	Cell Rep Med, 2025, 6(2):101929 Cells, 2025, 14(17)1386 Front Oncol, 2025, 15:1533059
S1025	Gefitinib (ZD1839)	Gefitinib ist ein EGFR-Inhibitor für Tyr1173, Tyr992, Tyr1173 und Tyr992 in den NR6wtEGFR- und NR6W-Zellen mit einer IC50 von 37 nM, 37 nM, 26 nM bzw. 57 nM. Diese Verbindung fördert Autophagy und Apoptosis von Lungenkrebszellen über die Blockade des PI3K/AKT/mTOR-Signalwegs.	Nat Commun, 2025, 16(1):7287 Nat Commun, 2025, 16(1):6451 Cell Rep Med, 2025, 6(2):101929
E4884	Icotinib Hydrochloride	Icotinib Hydrochloride (BPI-2009H) ist ein hochpotenter und selektiver epidermaler Wachstumsfaktorrezeptor-Tyrosinkinaseinhibitor (EGFR-TKI) mit einer IC50 von 5 nM, der zur Behandlung von nicht-kleinzelligem Lungenkrebs (NSCLC) eingesetzt wird.
S7786	Erlotinib (CP-358774)	Erlotinib ist ein EGFR-Inhibitor mit einer IC50 von 2 nM, der ">1000-fach empfindlicher für EGFR ist als menschliches c-Src oder v-Abl. Erlotinib induziert 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) ist ein oraler, potenter und selektiver Inhibitor von ErbBs (EGFR oder Her2), insbesondere von mutierten Formen von ErbBs. Es hemmt auch EGFR exon 20 NPH insertion, EGFR exon 20 ASV insertion, EGFR L858R und T790M mutations, Her2 exon 20 YVMA und EGFR WT A431 mit IC50-Werten von 20,4 nM, 20,4 nM, 1,1 nM, 7,5 nM bzw. 80,4 nM.	bioRxiv , 2023, 10.1101/2023.07.27.550902
S1023	Erlotinib (CP-358774) Hydrochloride	Erlotinib HCl ist ein EGFR-Inhibitor mit einer IC50 von 2 nM in zellfreien Assays, >1000-fach empfindlicher für EGFR als menschliches c-Src oder 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 ist ein hochselektiver HER2- und EGFR-Inhibitor mit IC50-Werten von 59 nM und 92 nM in zellfreien Assays; er hemmt KDR und Src schwach, ohne signifikante Hemmung von Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf und 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) ist ein oraler, potenter, selektiver, reversibler und ATP-kompetitiver niedermolekularer Inhibitor von ErbB-2 (auch HER2 genannt) mit IC50-Werten von 8 nM und 7 nM für ErbB-2 bzw. p95 HER2 in zellbasierten Assays, der eine etwa 500-fache Selektivität für HER2 gegenüber EGFR zeigt. Es besitzt eine potenzielle antineoplastische Aktivität.	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]