Nilotinib

SKU: orb1308331

Description

Nilotinib (AMN107) is an orally bioavailable, potent inhibitor of the Bcr-Abl tyrosine kinase. It demonstrates significant antitumor efficacy in both in vitro and in vivo models and is a key therapeutic agent for research on Imatinib-resistant chronic myelogenous leukemia (CML).

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 641571-10-0
• MW: 529.52
• Purity: >99.99% (May vary between batches)
• Formula: C₂₈H₂₂F₃N₇O
• SMILES: C(F)(F)(F)C=1C=C(C=C(NC(=O)C2=CC(NC=3N=C(C=CN3)C=4C=CC=NC4)=C(C)C=C2)C1)N5C=NC(C)=C5
• Target: Autophagy,Bcr-Abl
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:41.7 mg/mL (78.75 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2.6 mg/mL (4.91 mM)

Bioactivity

• Target IC50:
  HEK293 cells:0.5 μM|K562 cells:0.015 μM|K562 cells:0.022 μM|K562 cells:0.0039 μM|HCT116 cells:2.39 μM|BJ cells:12.8 μM|BaF3 cells:0.003 μM|KU812 cells:1.8 nM|Abl (WT):15 nM (cell free)|KBM5 cells:12 nM|CHO cells:4.7 μM|A549 cells:6.63 μM|Bcr-Abl:260 nM|Daoy cells:6 μM|H9C2 cells:21.33 μM
• In Vivo:
  METHODS: To test the antitumor activity in vivo, Nilotinib (25 mg/kg) and PD184352 (25 mg/kg) were administered by gavage to Balb/cJ mice bearing Ba/F3 allografts of BCR-ABL or BCR-ABLT315I once daily for twenty days. RESULTS: Nilotinib strongly inhibited the growth of BCR-ABL tumors, but not PD184352, nor did PD184352 enhance the growth inhibitory activity of Nilotinib. In contrast, BCR-ABLT315I tumors were insensitive to both Nilotinib and PD184352, but these drugs synergistically inhibited tumor growth.
• In Vitro:
  METHODS: Ba/F3 cells expressing wild-type or mutant Bcr-Abl were treated with Nilotinib for 72 h, and cell viability was measured by methanethiosulfonate-based viability assay. RESULTS: Nilotinib inhibited the growth of cells expressing wild-type Bcr-Abl with 20-fold higher potency than imatinib (IC50:13 vs. 260 nmol/L). Similar improvements were maintained in all imatinib-resistant mutants tested except T315I. METHODS: Melanoma cell line D04 was treated with Nilotinib (0.1-10 µM) for 3 h. Target protein expression levels were examined by Western Blot. RESULTS: Nilotinib stimulated robust MEK and ERK phosphorylation at concentrations as low as 100 nM.
• Cell Research:
  Ba/F3 cell lines were plated in triplicate and incubated with escalating concentrations of imatinib, AMN107, or BMS-354825 for 72 hours. Proliferation was measured using a methanethiosulfonate-based viability assay. IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges for IC50 and IC90 determinations were 0 to 2,000 nmol/L (imatinib and AMN107) or 0 to 32 nmol/L (BMS-354825). The imatinib concentration range was extended to 6,400 nmol/L for mutants with IC50 >2,000 nmol/L. The BMS-354825 concentration range was extended to 200 nmol/L for mutant T315I .
• Animal Research:
  The GIST xenograft lines GK1X, GK2X and GK3X in nude mice were established from GIST patients as described in our previous study . These xenograft lines were maintained by continual passage in BALB/cSLc-nu/nu mice. Mice bearing GK1X, GK2X and GK3X tumors (6–8 mice per group) were treated daily with vehicle or 40 mg/kg imatinib or nilotinib for 4 weeks. Tumor volume (TV) was determined from caliper measurements of tumor length (L) and width (w) according to the formula LW2/2. TV was determined every two to three days and on the day of evaluation. Mice were sacrificed and the percentage of tumor growth inhibition (TGI) was calculated as follows: TGI (%) = [1– (mean of treatment group tumor volume on evaluation day – mean of treatment group tumor volume on day 1)/(mean of control group tumor volume on evaluation day – mean of control group tumor volume on day 1)]×100 .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Tasigna, tyrosine kinase, inhibit, Nilotinib, Inhibitor, antitumor, AMN 107, AMN107, AMN-107, Autophagy, BcrAbl, Bcr-Abl

Compound Identifiers

PubChem CID

644241