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Nilotinib(AMN-107)

In stock
Catalog No.
A8232
Bcr-Abl kinase inhibitor,selective
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$55.00
In stock
100mg
$50.00
In stock
250mg
$70.00
In stock
500mg
$120.00
In stock
1g
$179.00
In stock

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Background

Nilotinib is a selective, oral inhibitor of tyrosine kinase with IC50 values of 20, 42, 31, 38, 29 and 41 nM for the autophosphorylation of native BCR-ABL (WT p210) and mutant BCR-ABL (E281K, E292K, F317L, M351T and F486S), respectively [1].

Nilotinib was designed based on the structure of imatinib and showed the superiority over imatinib in newly diagnosed or imatinib-resistant chronic myelogenous leukemia (CML). It was more potent than imatinib to wild-type BCR-ABL in a wide range of CML-derived and transfected cell lines. Nilotinib was also efficacious in gastrointestinal stromal tumors. Nilotinib showed inhibition activities in KIT mutant cells, including KITV560del, KITK642E and KITV560G (IC50 value of 108 nM). It also was effect to double mutations of KIT, such as KITV560del/V654A, KITV559D/D820Y, KITV560del/V654A (IC50: 192 nM) and KITV559D/D820Y (IC50: 297 nM). Besides that, Nilotinib exerted selective inhibition of PDGFRα and PDGFRβ. It suppressed cell proliferation with IC50 value of 0.54 nM in EOL-1 cells with constitutive activation of FIP1L1-PDGFRα [1, 2].

References:
[1] Weisberg E, Manley P, Mestan J, et al. AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. British Journal of Cancer, 2006, 94(12): 1765-1769.
[2] Blay J Y, Von Mehren M. Nilotinib: a novel, selective tyrosine kinase inhibitor//Seminars in oncology. WB Saunders, 2011, 38: S3-S9.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt529.53
Cas No.641571-10-0
FormulaC28H22F3N7O
SynonymsAMN-107; Tasigna; AMN107
Solubility≥26.5mg/mL in DMSO, ≥5mg/mL in EtOH with ultrasonic and warming, <2.31 mg/mL in H2O
Chemical Name4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide
SDFDownload SDF
Canonical SMILESCC1=C(C=C(C=C1)C(=O)NC2=CC(=CC(=C2)N3C=C(N=C3)C)C(F)(F)F)NC4=NC=CC(=N4)C5=CN=CC=C5
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

Cell experiment: [1]

Cell lines

CD34+ cells from individual patients with CML

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

5 μM, 16 hours

Applications

After 16 hours in culture with nilotinib, long enough for inhibition of CrkL phosphorylation but not for induction of apoptosis, the total CD34+ cell samples studied exhibited only partial and variable inhibition (range, 49% to 0% inhibition) of CrkL phosphorylation.

Animal experiment: [2]

Animal models

C57Bl/6J mice injected with 8093 lymphoma cells

Dosage form

Oral administration, 75 mg/kg, daily

Applications

Vehicle treated mice became moribund within 3 weeks of the transplantation. They showed clear symptoms of ALL. Nilotinib-treated mice lived statistically significantly longer as compared with the vehicle-treated mice. This result clearly indicated that nilotinib was very effective in inhibiting the proliferation of the leukemic cells in vivo.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Jørgensen H G, Allan E K, Jordanides N E, et al. Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells. Blood, 2007, 109(9): 4016-4019.

[2] Kaur P, Feldhahn N, Zhang B, et al. Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia. Mol Cancer, 2007, 6(10): 67-77.

Biological Activity

Description Nilotinib (AMN-107) is an inhibitor of Bcr-Abl with IC50 less than 30 nM.
Targets Bcr-Abl          
IC50 30 nM          

Quality Control

Chemical structure

Nilotinib(AMN-107)

Related Biological Data

Nilotinib
Histograms represent stereological quanti?cation of TDP-43 expressing cells. Asterisks indicate signi?cantly different to control or as indicated, mean + SEM, n=8, ANOVA, Neumann–Keuls multiple comparison.

Related Biological Data

Nilotinib

Related Biological Data

Nilotinib

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Nilotinib