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].
Références:
- [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]
All Product Categories
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ErbB4/HER4 Produits associés (25)
Produits associés (25)
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Protéines Recombinantes (10)
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EGFR-IN-12
0 ImagesEGFR-IN-12 is a 4,6-disubstituted pyrimidine and is a potent, ATP-competitive, irreversible and highly selective EGFR inhibitor with an IC50of 21 nM. EGFR-IN-12 also inhibits mutant EGFRL858R and EGFRL861Q with IC50s of 63 nM and 4 nM, respectively. EGFR-IN-12 displays strong selectivity for EGFR over HER4 (IC50 = 7640 nM) and a panel of 55 other kinases. EGFR-IN-12 induces cells apoptosis and has antitumor activity.
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Allitinib tosylate
0 ImagesSynonyms: AST-1306 (TsOH)Allitinib tosylate (AST-1306 (TsOH)) is an orally active and irreversible EGFR and ErbB2 inhibitor with IC50s of 0.5 and 3 nM, respectively. Allitinib tosylate also inhibits ErbB4 with an IC50 of 0.8 nM. Allitinib tosylate is an anilino-quinazoline compound and has anti-cancer activity
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BI-1622
0 ImagesBI-1622 is an orally active, potent and highly selective HER2 (ERBB2) inhibitor, with an IC50 of 7 nM. BI-1622 shows greater than 25-fold selectivity over EGFR. BI-1622 shows high antitumor efficacy in vivo in xenograft mouse tumor models with engineered H2170 and PC9 cells and had a favorable agent metabolism and pharmacokinetics profile.
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EGFR/ErbB-2/ErbB-4 inhibitor-3
0 ImagesCat. No.: HY-103440CAS No.: 881001-19-0EGFR/ErbB-2/ErbB-4 inhibitor-3 (compound 29) is a potent tyrosine kinase inhibitor with IC50s of 0.3, 1.1, 0.5, 2.5, 24 nM for erbB1, erbB2, erbB4, EGF, HER, respectively. EGFR/ErbB-2/ErbB-4 inhibitor-3 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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Epertinib hydrochloride
0 ImagesSynonyms: S-22611 hydrochlorideEpertinib (S-22611) hydrochloride 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 hydrochloride shows potent antitumor activity. Epertinib (hydrochloride) 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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STA-013
0 ImagesCat. No.: HY-179572Pureté: 99.18%STA-013 is a EphB tyrosine kinase inhibitor. STA-013 shows promising potency against EphB1 (IC50 = 0.69 µM), EphB2 (IC50 = 1.73 µM), and EphB4 (IC50 = 1.02 µM) tyrosine kinases. STA-013 results a inhibition of the EphB phosphorylated signal, coupled with increased p-AKT/AKT signaling, to suggest insulin signaling activation. STA-013 inhibits EphB tyrosine kinase by enhancing insulin receptor beta (IRβ) signaling, and decreasing TGF-β levels in the heart. STA-013 can be used for the study of type 2 diabetes and cardiac complications (diabetic cardiomyopathy).
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JNJ28871063 hydrochloride
0 ImagesJNJ28871063 hydrochloride is an orally active, highly selective and ATP competitive pan-ErbB kinase inhibitor with IC50 values of 22 nM, 38 nM, and 21 nM for ErbB1, ErbB2, and ErbB4, respectively. JNJ28871063 hydrochloride inhibits phosphorylation of functionally important tyrosine residues in both EGFR and ErbB2. JNJ28871063 hydrochloride crosses the blood-brain barrier and has antitumor activity in human tumor xenograft models that overexpress EGFR and ErbB2.
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CHMFL-EGFR-202
0 ImagesCHMFL-EGFR-202 is a potent, irreversible inhibitor of epidermal growth factor receptor (EGFR) mutant kinase, with IC50s of 5.3 nM and 8.3 nM for drug-resistant mutant EGFR T790M and WT EGFR kinases, respectively. CHMFL-EGFR-202 exhibits ～10-fold selectivity for EGFR L858R/T790M against the EGFR wild-type in cells. CHMFL-EGFR-202 adopts a covalent “DFG-in-C-helix-out” inactive binding conformation with EGFR, with strong antiproliferative effects against EGFR mutant-driven nonsmall-cell lung cancer (NSCLC) cell lines.
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TAS0728
0 ImagesTAS0728 is a potent, selective, orally active, irreversible and covalent-binding HER2 inhibitor, with an IC50 of 13 nM. TAS0728 also shows IC50s of 4.9, 8.5, 31, 65, 33, 25 and 86 nM for BMX、HER4、BLK、EGFR、JAK3、SLK and LOK respectively. Furthermore, TAS0728 exhibits robust and sustained inhibition of the phosphorylation of HER2, HER3, and downstream effectors.
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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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