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Nilotinib

Tyrosine kinase inhibitor; Inhibits BCR/ABL and ABL

STEMCELL Technologies Inc.

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Nilotinib is a second-generation inhibitor of the oncogenic tyrosine kinase BCR-ABL with IC₅₀ values of 19, 140, and 9,200 nM for wild-type, E255K, and T315I mutant forms of BCR-ABL, respectively (Kitagawa et al.; Verstovsek et al.; O'Hare). It binds to the ATP-binding pocket of ABL, with higher affinity than imatinib (Manley et al. 2006; Verstovsek et al.). It also has activity below 1 μM against discoidin domain receptors (DDR) -1 and -2, platelet-derived growth factor receptors (PDGFR) -α and -β, stem cell factor receptor (KIT), and colony-stimulating factor 1 receptor (CSF-1R; Manley et al. 2010).

CANCER RESEARCH

  • Inhibits cellular proliferation in many wild-type and mutant forms of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) cells (Verstovsek et al.; O'Hare).
  • Inhibits cell proliferation and progression through S phase in human lung cell line A549 through transcriptional changes in DNA helicase complex, cyclins, and cyclin-dependent kinases (Ji et al.).

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