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EGFR Epidermal Growth Factor Receptor

EGFR Inhibitors (33)

water-soluble

Cat.No. Product Name Information Product Citations Customer Reviews
S1023 Erlotinib HCl Erlotinib HCl is an HER1/EGFR inhibitor with IC50 of 2 nM.
S1025 Gefitinib (Iressa) Gefitinib (Iressa, ZD-1839) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively.
S1011 Afatinib (BIBW2992) BIBW2992 (Afatinib, Tomtovok, Tovok) irreversibly inhibits EGFR/HER2 including EGFRwt, EGFRL858R, EGFRL858R/T790M and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively.
S1143 AG-490 AG-490 (Tyrphostin B42) is an inhibitor of EGFR, ErbB2 and JAK2 with IC50 of 0.1 μM, 13.5 μM, and ~10 μM, respectively.
S2111 Lapatinib Lapatinib, used in the form of Lapatinib Ditosylate, is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM, respectively.
S4911 BMS-690514
S1028 Lapatinib Ditosylate (Tykerb) Lapatinib Ditosylate (GW572016, GW2016, Tykerb, Tyverb) is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM, respectively.
S1167 CP-724714 CP-724,714 is a potent, selective inhibitor of HER2/ErbB2 with IC50 of 10 nM and also inhibits EGFR with IC50 of 6.4 μM.
S2727 Dacomitinib (PF299804,PF-00299804) PF299804 is a potent, irreversible pan-ErbB inhibitor against ErbB1, ErbB2 and ErbB4 with IC50 of 6 nM, 45.7 nM and 73.7 nM, respectively.
S2728 AG-1478 (Tyrphostin AG-1478) AG-1478 (Tyrphostin AG-1478) is a selective EGFR inhibitor with IC50 of 3 nM.
Cat.No. Product Name Information Product Citations Customer Reviews
S1019 CI-1033 (Canertinib) CI-1033 is a potent inhibitor of EGFR and ErbB2 with IC50 of 1.5 nM and 9.0 nM, respectively.
S1194 CUDC-101 CUDC-101 is a potent multi-target inhibitor targeting HDAC, EGFR and HER2 with IC50 of 4.4 nM, 2.4 nM, and 15.7 nM, respectively.
S2150 Neratinib (HKI-272) Neratinib (HKI-272) is a highly selective HER2 and EGFR inhibitor with IC50 of 59 nM and 92 nM, respectively.
S1173 WZ4002 WZ4002 is a novel, mutant-selective EGFR inhibitor for EGFRL858R and EGFRL858R/T790M with IC50 of 2 nM and 8 nM, respectively.
S1392 Pelitinib (EKB-569) Pelitinib (EKB-569) is a potent EGFR inhibitor with IC50 of 38.5 nM.
S2192 AZD8931 AZD8931 is a reversible, ATP competitive inhibitor of EGFR, ErbB2 and ErbB3 with IC50 of 4 nM, 3 nM and 4 nM, respectively.
S2185 AST-1306 AST-1306 is a novel irreversible inhibitor of EGFR and ErbB4 with IC50 of 0.5 nM and 0.8 nM, respectively.
S2752 Arry-380 ARRY-380 is a potent and selective HER2 inhibitor with IC50 of 8 nM and also inhibits EGFR with IC50 of 4 μM.
S1079 PD153035 HCl PD153035 is a potent and specific inhibitor of EGFR with Ki and IC50 of 5.2 pM and 29 pM, respectively.
S1083 XL647 XL647 is a novel spectrum-selective kinase inhibitor for EGFR, ErbB2, KDR, Flt-4 and EphB4 with IC50 of 0.3 nM, 16 nM, 1.5 nM, 8.7 nM and 1.4 nM, respectively.
Cat.No. Product Name Information Product Citations Customer Reviews
S2755 ARRY334543 ARRY334543 is a selective and potent ErbB1 and ErbB2 inhibitor with IC50 of 7 nM and 2 nM, respectively.
S2867 WHI-P154 WHI-P154 is a potent JAK3 inhibitor with IC50 of 1.8 μM and also inhibits EGFR with IC50 of 4 nM.
S1179 WZ8040 WZ8040 is a novel mutant-selective irreversible EGFRT790M inhibitor.
S2205 OSI-420 OSI-420 is an active metabolite of Erlotinib which is an orally active EGFR inhibitor for inhibition of human EGFR and EGFR autophosphorylation with IC50 of 2 nM and 20 nM, respectively.
S1056 BMS-599626 (AC480) BMS-599626 (AC480) is a selective and efficacious inhibitor of HER1 and HER2 with IC50 of 20 nM and 30 nM, respectively.
S1486 AEE788 (NVP-AEE788) AEE788 is a potent inhibitor of EGFR and HER2/ErbB2 with IC50 of 2 nM and 6 nM and also inhibits VEGFR2 and Flt with IC50 of 77 nM and 59 nM, respectively.
S2784 TAK-285 TAK-285 is a novel dual HER2 and EGFR inhibitor with IC50 of 17 nM and 23 nM, respectively.
S2826 Desmethyl Erlotinib (CP-473420) Desmethyl Erlotinib (CP-473420) is a free base of OSI-420, which is an active metabolite of Erlotinib which is an orally active EGFR inhibitor for human EGFR with IC50 of 2 nM.
S8009 AG 18 (Tyrphostin 23) AG 18 inhibits EGFR with IC50 of 35 μM.
S1170 WZ3146 WZ3146 is a mutant-selective irreversible inhibitor of EGFR(L858R) and EGFR(E746_A750) with IC50 of 2 nM and 2 nM, respectively.
Cat.No. Product Name Information Product Citations Customer Reviews
S2733 AV-412 AV-412 is a second-generation, orally bioavailable dual EGFR/HER2 tyrosine kinase inhibitor.
S2895 Tyrphostin 9 (SF 6847) SF 6847 is an inhibitor of EGFR with IC50 of 460 μM.
S2922 Icotinib Icotinib is a potent and specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with IC50 of 5 nM.
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All EGFR Inhibitors

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]

References

[1] Han, W., and Lo, H-W. Mini Review: Landscape of EGFR signaling network in human cancers: biology and therapeutic response in relation to receptor subcellular locations. Cancer Letters 2012; 318: 124-134.
[2] Larsen, A.K., Ouaret, D., El Ouadrani, K., and Petitprez, A. Targeting EGFR and VEGF(R) pathway cross-talk in tumor survival and angiogenesis. Pharmacology and Therapeutics 2011; 131: 80-90.
[3] Vivancoa, I and Mellinghoff, I.K. Epidermal growth factor receptor inhibitors in oncology. Current Opinion in Oncology 2010; 22: 573–578.

Tags: EGFR inhibition | EGFR cancer | EGFR tumor | EGFR activation | EGFR signaling pathway | EGFR phosphorylation | EGFR targets | EGFR inhibitor drugs | EGFR inhibitors cancer | EGFR assay | EGFR activity | EGFR inhibitors list | EGFR inhibitor review