A chimeric BCR-ABL oncogene is obtained by the fusion of Abelson (ABL) tyrosine kinase (TK) gene and break-point cluster (BCR) gene, and here TK has been related to pathogenesis of CML (Chronic Myelogenous Leukemia), 90% of this debilitating disease involves chromosomal abnormalities leading to formation of so-called Philadelphia chromosome. As there is a confirmed participation of BCR-ABL TK in PH+ CML, different inhibitors that target this TK have registered remarkable success in treatment of CML and among them Nilotinib bcr-abl inhibitor is the most valuable one. It is a form of tyrosine kinase inhibitor and is a hydrochloride monohydrate salt. 

In the form of Nilotinib AMN-107, Novartis has produced a very important and effective therapeutic tool against PH+ ALL and CML. It comes in the market in a form of 400 mg tablet for oral administration showing a trade name of Tasigna over it. One can purchase Nilotinib for laboratory and research purposes. The reasonable price has facilitated its uses in laboratory. Researchers can easily buy Nilotinib from supplier Nilotinib by paying Nilotinib price that is around $60 for a 100 mg packet and this price may vary from Nilotinib supplier to supplier. Nilotinib IC50 value is found to be <12 nM for an efficient inhibition of BCR-ABL TK, it can be more than 12 nM for PDGF and c-Kit inhibition. AMN-107 structure shows that it has a benzamide group. Nilotinib solubility is better in DMSO that is around 50 mg/mL while this drug is poorly soluble in ethanol and water.
The initial Nilotinib clinical trial has seen its chemical modification and characterization to increase its specificity rendering intact its inhibition capacity [1]. Mechanism of Nilotinib involves its binding to TKs’ ATP binding sites thus rendering them in inactivated form. As the reports revealing the resistance causing mutations to Nilotinib came to light, this drug becomes more patient specific in use [2]. A few of point mutations were identified by the genetic screening and those were found to be related to resistance developed against Nilotinib [3].
As compared to the traditional therapeutic drugs for CML i.e. Imatinib and Dasatinib, Nilotinib was generated much later and caused suppression in their popularity owing to its low toxicity profile and better Nilotinib stability [4]. The knowledge of chemical differences of Nilotinib with Dasatinib and Imatinib has made its characterization more convenient leading to some extensive developments [5]. A recent research report has described the differential effects of Imatinib, Dasatinib and Nilotinib on the natural killer cells [6]. 

Nilotinib clinical trials have mostly involved its use in treatment of Imatinib-resistant PH+ ALL and CML [7]. After successful studies under phase I, Nilotinib was used against chronic CML patients under phase II who were showing intolerance against Imatinib treatment [8-10]. After the success that acted as a leading edge for patients of phase II PH+ CML [11], a recent research has promoted its use over Imatinib as a better therapeutic approach in clinical trials phase III against patients of PH+ CML [12]. Nilotinib has got preference over traditional Imatinib not only against advanced CML patients but also newly diagnosed CML patients has seen good results under phase III trials [13].
Apart from its remarkable success in PH+ CML patients, Nilotinib was employed for treatment of GISTs (gastrointestinal stromal tumors) and according to a recent report it was found to be very successful in GISTs patients under clinical trials phase III [14]. The current clinical studies by the Novatis, the drug manufacturers, involves the use of AMN-107 in clinical studies under phase II for patients of CML (NCT00129740) and under phase III trials, open-label studies in patients of GISTs (ENESTg1) (NCT00785785).  

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.