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Merck
CN

SML4231

Neratinib

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

Synonym(s):

(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

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About This Item

Empirical Formula (Hill Notation):
C30H29ClN6O3
CAS Number:
Molecular Weight:
557.04
MDL number:
NACRES:
NA.21
Assay:
≥98% (HPLC)
Form:
powder
Quality level:
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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

Quality Level

assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear (warmed)

storage temp.

2-8°C

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.

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Vidya Sankarapandian et al.
Pathology, research and practice, 263, 155607-155607 (2024-09-27)
Breast cancer is a heterogeneous disease with complex molecular pathogenesis. Overexpression of several tyrosine kinase receptors is associated with poor prognosis, therefore, they can be key targets in breast cancer therapy. Tyrosine kinase inhibitors (TKIs) have emerged as leading agents
Nadia Godin-Heymann et al.
Molecular cancer therapeutics, 7(4), 874-879 (2008-04-17)
Patients with non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) kinase domain tend to respond well to the tyrosine kinase inhibitors, gefitinib and erlotinib. However, following clinical response, these patients typically relapse within
Cai-Hong Yun et al.
Proceedings of the National Academy of Sciences of the United States of America, 105(6), 2070-2075 (2008-01-30)
Lung cancers caused by activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to small molecule tyrosine kinase inhibitors (TKIs), but the efficacy of these agents is often limited because of the emergence of drug resistance conferred

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