ErbB4/HER4
ErbB4/HER4 is an EGFR/ErbB-family receptor tyrosine kinase that mediates responses to neuregulins and other EGF-like growth factors[1]. Mechanistically, ErbB4 regulates cardiovascular and neural development and mammary gland differentiation through ligand-dependent receptor signaling[1]. Alternative splicing generates four structurally and functionally distinct ErbB4 isoforms, defined by extracellular juxtamembrane domains and cytoplasmic tails[1]. Compared with related ErbB receptors, ErbB4 shows isoform-specific signaling: both cytoplasmic isoforms couple to Shc-MAPK, whereas one isoform cannot activate PI3K-Akt[1]. In mammary models, NRG3 regulates epithelial progenitor cell positioning, and activation of ErbB4 JM-a CYT-1 leads to mammary epithelial cell spreading and migration[2]. In 3D mammary organoids, culture conditions including Neuregulin1 and R-spondin 1 support maintenance and expansion for 2.5 months[3]. In cancer research, ERBB4 has context-dependent roles, with ERBB4 homodimers reviewed as tumor suppressive and ERBB4-EGFR or ERBB4-ERBB2 heterodimers reviewed as oncogenic[4]. For inhibitor design, structural work defined activation and inhibition mechanisms of the HER4/ErbB4 kinase, and imidazothiazole derivatives were reported as potent and selective ErbB4 inhibitors[5][6].
References:
- [1]. Junttila TT, et al. Erbb4 and its isoforms: selective regulation of growth factor responses by naturally occurring receptor variants. Trends Cardiovasc Med. 2000 Oct;10(7):304-10. [Content Brief]
- [2]. Kogata N, et al. Neuregulin-3 regulates epithelial progenitor cell positioning and specifies mammary phenotype. Stem Cells Dev. 2014 Nov 15;23(22):2758-70. [Content Brief]
- [3]. Jardé T, et al. Wnt and Neuregulin1/ErbB signalling extends 3D culture of hormone responsive mammary organoids. Nat Commun. 2016 Oct 26;7:13207. [Content Brief]
- [4]. Lucas LM, et al. The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein. Pharmacol Rev. 2022 Jan;74(1):18-47. [Content Brief]
- [5]. Qiu C, et al. Mechanism of activation and inhibition of the HER4/ErbB4 kinase. Structure. 2008 Mar;16(3):460-7. [Content Brief]
- [6]. Zaraei SO, et al. Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors. Eur J Med Chem. 2021 Nov 15;224:113674. [Content Brief]
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ErbB4/HER4 Related Products (28)
Related Products (28)
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Recombinant Proteins (10)
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Epertinib
0 ImagesCat. No.: HY-107367CAS No.: 908305-13-5Synonyms: S-22611Epertinib (S-22611) is a potent, orally active, reversible, and selective tyrosine kinase inhibitor of EGFR, HER4 and HER2, with IC50s of 1.48 nM, 2.49 nM and 7.15 nM, respectively. Epertinib shows potent antitumor activity. Epertinib is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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Anti-Mouse E-Cadherin/CD324 Antibody (DECMA-1)
0 ImagesCat. No.: HY-P990248Purity: 98.53%Anti-Mouse E-Cadherin/CD324 Antibody (DECMA-1) is an anti-mouse E-Cadherin/CD324 IgG1 monoclonal antibody. Anti-Mouse E-Cadherin/CD324 Antibody (DECMA-1) can downregulate the HER signaling axis and PI3K/Akt/mTOR signaling pathway. Anti-Mouse E-Cadherin/CD324 Antibody (DECMA-1) can inhibit the proliferation of tumor cells and induce their apoptosis. Anti-Mouse E-Cadherin/CD324 Antibody (DECMA-1) can be used for researches on cancer and inflammation conditions such as breast cancer, chronic compression injury (CCI) and asthma.
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TAS-121
0 ImagesCat. No.: HY-164392CAS No.: 1451370-01-6TAS-121 is an orally active, selective, covalent, third-generation mutant EGFR-tyrosine kinase inhibitor (EGFR-TKI). TAS-121 inhibits the L858R mutation (IC50=1.7 nM), Ex19del mutation (IC50=2.7 nM), L858R/T790M mutation (IC50=0.56 nM) and Ex19del/T790M mutation (IC50=1.1 nM) and wild-type EGFR (IC50=8.2 nM). TAS-121 inhibits HER2 and HER4 with IC50s of 110 and 2.6 nM, respectively. TAS-121 inhibits phosphorylation of EGFR and its downstream signaling targets to block cell proliferation. TAS-121 induces apoptosis and displays antitumor activity in SW48 (EGFR G719S) and NCI-H1975 (EGFR L858R/T790M) xenograft models.
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HER4/HER2-IN-1
0 ImagesCat. No.: HY-178119HER4/HER2-IN-1 (Compound 4b) is a HER4/HER2 inhibitor. HER4/HER2-IN-1 inhibits the proliferation of HER2-positive cells. HER4/HER2-IN-1 reduces the total expression level of HER2 in A431 cells, while the phosphorylated HER2 (p-HER2) does not decrease. HER4/HER2-IN-1 lowers the level of cell cycle protein D1 (cyclin D1) and stimulates the cleavage of PARP. HER4/HER2-IN-1 can be used for the study of cancer, such as breast cancer.
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SYR127063
0 ImagesCat. No.: HY-111250CAS No.: 871026-18-5SYR127063 is a potent and selective human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor with an IC50 of 11 nM. SYR127063 binds to the active site of the HER2 kinase domain in an ATP-competitive manner, thereby preventing the formation of the conserved salt bridge required for kinase activation. SYR127063 can be used in research related to breast cancer, ovarian cancer and gastric cancer.
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