Find Lapatinib Inhibitor, Afatinib Inhibitor, Neratinib Inhibitor on Industry Directory, Reliable Manufacturer/Supplier/Factory from China.

Inquiry Basket (0)
Home > Products > Protein Tyrosine Kinase > HER2 Inhibitor > Neratinib (HKI-272) 698387-09-6

Neratinib (HKI-272) 698387-09-6

Product Description

.cp_wz table {border-top: 1px solid #ccc;border-left:1px solid #ccc; } .cp_wz table td{border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc;border-bottom: 1px solid #ccc; padding: 5px 0px 0px 5px;}


Molecular Weight:

557.04 Neratinib (HKI-272) is a highly selective HER2 and EGFR Inhibitor with IC50 of 59 nM and 92 nM; weakly inhibits KDR and Src, no significant inhibition to Akt, CDK1/2/4, IKK-2, MK-2, PDK1, c-Raf and c-Met. Phase 3.


Biological Activity


Neratinib weakly inhibits tyrosine kinases KDR and Src with IC50 of 0.8
μM and 1.4 μM, respectively, being 14- and 24-fold less active compared
with HER2. Neratinib displays no activity against other serine-threonine
kinases such as Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1,
IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, as well as the tyrosine kinase
c-Met.


Neratinib selectively inhibits the proliferation of 3T3 cells
transfected with the HER2 (3T3/neu), as well as two Other
HER-2-overexpressing SK-Br-3 and BT474 cells with IC50 values of 2-3 nM,
displaying >230-fold potency compared with non-transfected 3T3 cells
as well as MDA-MB-435 and SW620 which are EGFR- and HER2-negative.
Neratinib also inhibits the proliferation of EGFR-dependent A431 cells
with an IC50 of 81 nM.


Neratinib reduces HER2 receptor
autophosphorylation in BT474 cells with an IC50 of 5 nM, and
EGF-dependent phosphorylation of EGFR in A431 cells with IC50 of 3 nM.
Blocking of HER-2 by Neratinib results in inhibition of downstream MAPK
and Akt pathways with IC50 of 2 nM, more potently than Trastuzumab.
Neratinib inhibits the cyclin D1 expression and the phosphorylation of
the Rb-susceptibility gene production in BT474 cells with IC50 of 9 nM,
leading to G1-S arrest and ultimately decreased cell proliferation.


Oral administration of Neratinib significantly inhibits the growth of
3T3/neu xenografts, with inhibition of 34%, 53%, 98%, and 98% at dose of
10, 20, 40, and 80 mg/kg/day, respectively. Consistent with the
inhibition of HER-2 phosphorylation by 84% within 1 hour of
administration at 40 mg/kg/day, Neratinib inhibits the growth of BT474
xenografts by 70-82%, 67%, and 93% at dose of 5, 10, and 40 mg/kg/day,
respectively.


Neratinib is also effective against SK-OV-3 xenografts
with inhibition of 31% and 85% at 5 and 60 mg/kg/day, respectively.
Neratinib is less potent against EGFR-dependent A431 xenografts than
HER-2-dependent tumors, with 32% and 44% inhibition at 5 and 20
mg/kg/day, respectively. Neratinib displays little activity against
MCF-7 and MX-1 xenografts expressing low levels of HER-2 and EGFR, with
only 28% inhibition at 80 mg/kg/day, suggesting that Neratinib has
selective activity for cells expressing HER-2 or EGFR.






Cell-free autophosphorylation assay using time-resolved fluorometry


Neratinib is prepared as 10 mg/mL stocks in DMSO and diluted in 25 mM
HEPES (pH 7.5; 0.002 ng/mL-20 μg/mL). Purified recombinant COOH-terminal
fragments of HER2 (Amino Acids 676-1255) or epidermal growth factor
receptor (EGFR) (amino acids 645-1186) [diluted in 100 mM HEPES (pH 7.5)
and 50% glycerol] is incubated with increasing concentrations of
Neratinib in 4 mM HEPES (pH 7.5), 0.4 mM MnCl2, 20 μM sodium
vanadate, and 0.2 mM DTT for 15 minutes at room temperature in 96-well
ELISA plates.


The kinase reaction is initiated by the addition of 40 μM
ATP and 20 mM MgCl2 and allowed to proceed for 1 hour at room
temperature. Plates are washed, and phosphorylation is detected using
Europium-labeled anti-phospho-tyrosine antibodies (15 ng/well). After
washing and enhancement steps, signal is detected using a Victor2
fluorescence reader (excitation wavelength 340 nm, emission wavelength
615 nm). The concentration of Neratinib that inhibits receptor
phosphorylation by 50% (IC50) is calculated from inhibition curves.

Method

Cells are exposed to various concentrations of Neratinib for 2, or 6
days. Cell proliferation is determined using sulforhodamine B, a protein
binding dye. Briefly, cells are fixed with 10% trichloroacetic acid and
washed extensively with water. Cells are then stained with 0.1%
sulforhodamine B and washed in 5% acetic acid. Protein-associated dye is
solubilized in 10 mM Tris, and absorbance is measured at 450 nM. The
concentration of Neratinib that inhibits cell proliferation by 50%
(IC50) is determined from inhibition curves.

Contact us if you need more details on 698387-09-6. We are ready to answer your questions on packaging, logistics, certification or any other aspects about Neratinib 698387-09-6、HKI-272 698387-09-6. If these products fail to match your need, please contact us and we would like to provide relevant information.

Product Categories : Protein Tyrosine Kinase > HER2 Inhibitor