Cell Signaling Technology

Product Pathways - Tyrosine Kinase / Adaptors

Nilotinib #12209

Molecular Formula:
C28H22F3N7O
Molecular Weight:
529.52 g/mol
Purity:
>99%

Directions for Use

Nilotinib is supplied as a lyophilized powder. For a 5 mM stock, reconstitute the 5 mg in 1.89 ml DMSO. Working concentrations and length of treatment can vary depending on the desired effect, but it is typically used at 10-1000 nM for 2-72 hr. Nilotinib is soluble in DMSO at 50 mg/ml; very poorly soluble in ethanol and water with maximum solubility in water at ~10-20 µM.

Western Blotting

Western Blotting

Western blot analysis of extracts from K-562 cells, untreated (-) or treated (+) with Nilotinib (1000 nM, 24 hr), using PathScan® Bcr/Abl Activity Assay: Phospho-c-Abl, Phospho-Stat5, and Phospho-CrkL Multiplex Western Detection Cocktail #5300 to detect inhibition of phospho-Bcr-Abl, phospho-Stat5, and phospho-CrkL.

Structure

Structure

Chemical structure of nilotinib.

Background

Nilotinib (AMN-107) is a novel tyrosine kinase inhibitor that potently inhibits Bcr-Abl. Nilotinib is more effective than imatinib at decreasing the proliferation and viability in cells expressing wild-type Bcr-Abl and is active against many imatinib-resistant Bcr-Abl mutants, with the exception of T315I (1-4). Nilotinib has been shown to inhibit Abl activity in cells expressing wild-type Abl and imatinib-resistant mutant Abl, with ~20-fold greater potency than imatinib. Nilotinib is similarly effective at inhibiting Abl autophosphorylation (3). Research studies have demonstrated that nilotinib treatment of Bcr-Abl-expressing K-562 cells attenuates Stat5 and CrkL phosphorylation, decreases Bcl-xL and c-Myc expression, induces p27 and Bim expression, and induces PARP cleavage. Many of these effects are enhanced by cotreatment with the histone deacetylase inhibitor LBH589 (5).

  1. Weisberg, E. et al. (2006) Br J Cancer 94, 1765-9.
  2. Golemovic, M. et al. (2005) Clin Cancer Res 11, 4941-7.
  3. O'Hare, T. et al. (2005) Cancer Res 65, 4500-5.
  4. Weisberg, E. et al. (2005) Cancer Cell 7, 129-41.
  5. Fiskus, W. et al. (2006) Blood 108, 645-52.

Application References

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For Research Use Only. Not For Use In Diagnostic Procedures.

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