General description
Neratinib is a compound featuring a quinolone core, with a lipophilic 2-pyridinylmethyl moiety at the para-position of the aniline and a lipophilic chlorine atom at the meta-position. These structural elements enhance its activity against human epidermal growth factor receptor 2 (HER2).
Application
Neratinib may be used to study its anti-proliferative effects in gastric adenocarcinoma cells.
Biochem/physiol Actions
Irreversible pan-HER inhibitor, covalently targets EGFR/HER2/HER4, providing sustained signaling blockade and clinical benefit in HER2-positive breast cancer.
Neratinib (HKI-272), an oral, potent, irreversible pan-HER tyrosine kinase inhibitor, targets EGFR, HER2, and HER4 by covalently binding specific cysteine residues (Cys773/EGFR, Cys805/HER2) within the ATP-binding pocket. This mechanism provides prolonged target inhibition, effectively blocking HER phosphorylation (IC50 ~3-5 nM) and downstream MAPK/Akt signaling (IC50 ~2 nM). Consequently, it reduces cyclin D1/Rb phosphorylation (IC50 ~9 nM) and induces G1-S arrest and apoptosis in sensitive cell lines (e.g., BT474, SKBr3, A431) at low nM concentrations, underpinning its use against HER2-driven cancers.
Neratinib (HKI-272), an oral, potent, irreversible pan-HER tyrosine kinase inhibitor, targets EGFR, HER2, and HER4 by covalently binding specific cysteine residues (Cys773/EGFR, Cys805/HER2) within the ATP-binding pocket. This mechanism provides prolonged target inhibition, effectively blocking HER phosphorylation (IC50 ~3-5 nM) and downstream MAPK/Akt signaling (IC50 ~2 nM). Consequently, it reduces cyclin D1/Rb phosphorylation (IC50 ~9 nM) and induces G1-S arrest and apoptosis in sensitive cell lines (e.g., BT474, SKBr3, A431) at low nM concentrations, underpinning its use against HER2-driven cancers.
| Quality Level | 100 |
| assay | ≥98% (HPLC) |
| form | powder |
| color | white to beige |
| solubility | DMSO: 2 mg/mL, clear (warmed) |
| storage temp. | 2-8°C |
| SMILES string | CN(C)C/C=C/C(NC(C=C1C(NC2=CC(Cl)=C(C=C2)OCC3=NC=CC=C3)=C4C#N)=C(C=C1N=C4)OCC)=O |
