Philadelphia chromosome is composed by fusion of a tyrosine kinase ABL (Abelson) and BCR (break point cluster) gene during the cross linking of chromosomes in meiosis. This Philadelphia chromosome promotes fusion protein that functions in an uncontrolled manner as a tyrosine kinase making it an oncoprotein. This fusion oncoprotein is involved in causing CML i.e., chronic myelogenous leukemia in 90 % of patients of this disease. Due to the involvement of this fusion protein in CML, it is being targeted in lots of research going on for cancer therapeutics. Nilotinib bcr-abl inhibitor is one these inhibitors being used against CML.


Nilotinib AMN-107 has been developed by Novartis for the patients of CML and ALL who are Ph+. Nilotinib structure shows to be a hydrochloride monohydrate salt and contain a benzamide group in it. It is soluble in DMSO up to 50 mg/ml whereas Nilotinib solubility is poor in water and ethanol. Nilotinib IC50 is less than 12 for BCR-ABL inhibition while for c-Kit and PDGF it is more than 12nM. One can buy Nilotinib with Nilotinib price of $60 for a packet of 400mg and varies from one Nilotinib supplier to the other.
Research on Nilotinib is being done its structure modification so as to increase its efficiency [1]. Mechanism by which the drug acts involves binding of the drug at ATP binding site on the tyrosine kinase and obviating the downstream cascade that causes the cells to proliferate or grow by following various pathways. In some patients development of resistance has made the drug more restricted for specific patients [2]. Some point mutations have been found in Ph+ patients in the gene against this drug [3] however Nilotinib is superior to the already discovered medicines that were being employed against CML e.g., Dasatinib and Imatinib, as it is less toxic and more stable than those drugs mentioned above [4]. There is also some chemical differences between Nilotinib and the other 2 drugs, Imatinib and Dasatinib, as a result of it is facilitating a lot of development related to this drug [5]. Recently effects of all the three drugs on NK (Natural killer) cells are being observed in a differential manner [6].

Nilotinib clinical trials are being done on GISTs and additionally on CML patients. It is mostly utilized in Imatinib resistant Ph+ patients of CML and ALL [7]. In this regards Nilotinib has been studied in phase I and phase II clinical trials on chronic CML patients [8-10]. Being successful in the initial phases of clinical trials [11], it has been promoted to phase III clinical trials in Ph+ CML patients [12]. Nilotinib is not only studied against chronic CML patients however it has additionally shown good results in newly diagnosed CML patients in clinical trials phase III [13].
Along with its successful results in clinical trials associated with CML, this drug has been used in the patients of gastrointestinal stromal tumors (GIST) too where it has shown quite efficient results in phase III clinical trials [14]. Currently clinical studies are going on by Novartis against the patients of CML in phase II  (NCT00129740)and open label studies in phase III in the patients of gastrointestinal stromal tumors i.e., GISTs (ENESTg1) (NCT00785785). Due to the successful clinical trials the drug is anticipated to be at the forefront for therapy against cancer.


1. Weisberg, E.e.a., AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. British Journal of Cancer, 2006. 94: p. 1765-1769.
2. Ray, A.e.a., Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study. Blood, 2007. 109(11): p. 5011-5015.
3. Bubnoff, N.V.e.a., BCR-ABL resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor Nilotinib (AMN107). Blood, 2006. 108: p. 1328-1333.
4. Bradeen, H.A.e.a., Comparison of imatinib mesylate, dasatinib (BMS-354825), and nilotinib (AMN107) in an N-ethyl-N-nitrosourea (ENU)–based mutagenesis screen: high efficacy of drug combinations. Blood, 2006. 108: p. 2332-2338.
5. Rix, U.e.a., Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood, 2007. 110(12): p. 4055-4063.
6. Salih, J.e.a., The BCR/ABL-inhibitors imatinib, nilotinib and dasatinib differentially affect NK cell reactivity. Int J Cancer, 2010. 127(9): p. 2119-28.
7. Kantarjian, H.e.a., Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med., 2006. 354(24): p. 2542-51.
8. Kantarjian, H.e.a., Nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood, 2011. 117(4): p. 1141-1145.
9. Kantarjian, H.e.a., Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood, 2007. 110(10): p. 3540-3546.
10. Coutre, P.L.e.a., Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood, 2008. 111(4): p. 1834-1839.
11. Rosti, G.e.a., Nilotinib for the frontline treatment of Ph+ chronic myeloid leukemia. Blood, 2009. 114(24): p. 4933-4938.
12. Kantarjian, H.M.e.a., Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. The Lancet Oncology, 2011. 12(9): p. 841-851.
13. Saglio, G.e.a., Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia. N Engl J Med, 2010. 362: p. 2251-2259.
14. Reichardt, P.a.M., M., Clinical Experience to Date With Nilotinib in Gastrointestinal Stromal Tumors. Seminars in Oncology, 2011. 38(1): p. S20-S27.

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