SML4231

Neratinib

≥98% (HPLC), powder, pan-HER inhibitor

• Synonym(e): (2E)-N-[4-[[3-Chloro-4-(2-pyridinylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide, 4-Dimethylamino-but-2-enoic acid {4-[3-chloro-4-(pyridin-2-ylmethoxy)phenylamino]-3-cyano-7-ethoxy-quinolin-6-yl}-amide, (E)-N-[4-[3-Chloro-4-[(2-pyridinyl)methoxy]anilino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide, (E)-N-[4-[[3-Chloro-4-((pyridin-2-yl)methoxy)phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)-2-butenamide, HKI-272, HKI 272
• Empirische Formel (Hill-System): C₃₀H₂₉ClN₆O₃
• CAS-Nummer: 698387-09-6
• Molekulargewicht: 557.04
• MDL number: MFCD09752958
• NACRES: NA.21
• UNSPSC Code: 12352200
• Assay: ≥98% (HPLC)
• Form: powder

Eigenschaften

• Quality Segment: 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

Beschreibung

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.

Sicherheitshinweise

• Piktogramme: GHS08
• Signalwort: Warning
• Gefahrencodes: H361d
• Sicherheitshinweise: P201 - P202 - P280 - P308 + P313 - P405 - P501
• Hazard Classifications: Repr. 2
• Lagerklasse: 11 - Combustible Solids
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable