Nilotinib - chemotherapy agent

Nilotinib is a selective Bcr/Abl tyrosine kinase inhibitor. This type of medicine is used in treatment of leukemia (specifically chronic myeloid leukemia.) Nilotinib is considered a "second-generation" Bcr/Abl tyrosine kinase inhibitor, building on the success of imatinib. Because many patients develop resistance to imatinib, there is excitement about nilotinib. A recent research report concluded it has "great potential" for leukemia treatment.

Nilotinib is an analog of imatinib with similar multiple kinase targets, but without inhibition of the Src gene. (This gene regulates tyrosine kinase proteins that in turn affect whether cells multiply or die.) Tyrosine kinase inhibitors interfere with cell communication and growth. They have been of great interest to scientists in recent years who hope to use them as an option to treat cancer.

The "binding mode" of nilotinib is energetically more favorable than that of imatinib. This results in a more selective targeting of the malignancy. Nilotinib has been shown to have an approximately 20-fold increased potency in kinase and proliferation assays compared to imatinib. This is especially important for older patients and they tend to have trouble tolerating imatinib treatment. The higher dosages required for imatinib make it tough; nilotinib is hoped to alleviate the side effects but still be effective.

Researchers have been interested in aurora kinases as targets for cancer therapy and seveal drugs are in development. Oncogenic BCR-ABL tyrosine kinase, which is deregulated in as many as 95% of chronic myeloid leukemia (CML) patients and in ~20% of adult Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) patients. ABL kinase domain mutations have been implicated in the resistance to imatinib mesylate of Philadelphia-positive (Ph+) leukemia patients.

Mast cells in tumors are affected by the new class of anti-cancer agents called kinase inhibitors, which includes nilotinib. Inside the body, mast cells regulate t-cells, promote blood clots, and enable the growth of blood vessels. The kinase inhibitors are considered a form or "targeted cancer therapy" because they are selective in the type of cells they affect.