Nilotinib(AMN-107) (Synonyms: AMN107) |
| رقم الكتالوجGC14129 |
Nilotinib(AMN-107) is a selective oral tyrosine kinase inhibitor that inhibits the autophosphorylation of native Bcr-Abl (WT p210) and mutant Bcr-Abl (E281K, E292K, F317L, M351T, and F486S) with IC50 values of 20, 42, 31, 38, 29, and 41nM, respectively.
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Cas No.: 641571-10-0
Sample solution is provided at 25 µL, 10mM.
Nilotinib(AMN-107) is a selective oral tyrosine kinase inhibitor that inhibits the autophosphorylation of native Bcr-Abl (WT p210) and mutant Bcr-Abl (E281K, E292K, F317L, M351T, and F486S) with IC50 values of 20, 42, 31, 38, 29, and 41nM, respectively[1]. Nilotinib inhibits lymphocyte-specific protein tyrosine kinase (LCK) with an IC50 of 550nM[2]. Nilotinib is an aminopyrimidine-based high-affinity ATP-competitive inhibitor[3].
In vitro, treatment of CD8+ T cells with Nilotinib (4µM) for 0-48h significantly inhibited PHA/IL-2-stimulated cell proliferation, downregulated the expression of CD8+ T cell activation markers CD69 and CD25, and reduced the phosphorylation of ERK 1/2 and LCK proteins[4]. Nilotinib (5µM) treatment of CD34+ cells from chronic myeloid leukemia (CML) patients for 16h inhibited CrkL phosphorylation but did not induce apoptosis[5].
In vivo, oral treatment of gastrointestinal stromal tumor (GIST) mice with Nilotinib (40mg/kg/day) for 4 weeks inhibited tumor growth by 69.6%, 85.3% and 47.5% in GK1X, GK2X and GK3X xenograft lines, respectively[6]. Oral treatment of leukemia mice with Nilotinib (75mg/kg/day) for 30 days significantly prolonged the survival of the mice, and visible lymphoma masses disappeared within six days of treatment, and the number of leukemia cells in the peripheral blood was significantly reduced[7].
References:
[1] Weisberg E, Manley P, Mestan J, et al. AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL[J]. British journal of cancer, 2006, 94(12): 1765-1769.
[2] Blake S J, Lyons A B, Hughes T P. Nilotinib inhibits the Src-family kinase LCK and T-cell function in vitro[J]. Journal of cellular and molecular medicine, 2009, 13(3): 599.
[3] Swords R, Mahalingam D, Padmanabhan S, et al. Nilotinib: optimal therapy for patients with chronic myeloid leukemia and resistance or intolerance to imatinib[J]. Drug design, development and therapy, 2009: 89-101.
[4] Chen J, Schmitt A, Chen B, et al. Nilotinib hampers the proliferation and function of CD8+ T lymphocytes through inhibition of T cell receptor signalling[J]. Journal of cellular and molecular medicine, 2008, 12(5b): 2107-2118.
[5] Jørgensen H G, Allan E K, Jordanides N E, et al. Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells[J]. Blood, 2007, 109(9): 4016-4019.
[6] Sako H, Fukuda K, Saikawa Y, et al. Antitumor effect of the tyrosine kinase inhibitor nilotinib on gastrointestinal stromal tumor (GIST) and imatinib-resistant GIST cells[J]. PloS one, 2014, 9(9): e107613.
[7] Kaur P, Feldhahn N, Zhang B, et al. Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia[J]. Molecular cancer, 2007, 6: 1-11.
| Cell experiment [1]: | |
Cell lines | CD8+ T cells |
Preparation Method | CD8+ T cells were labelled with CFSE at a final concentration of 1μM for 10min. at 37°C. Then, the cells were washed with ice-cold culture medium for three times and resuspended in culture medium. 4μM Nilotinib was added at different time points as indicated (0h, 24h and 48h). CD8+ T cells untreated with Nilotinib served as control. After 96 hrs of stimulation with PHA and IL-2, the proliferation of cells was measured by flow cytometry. |
Reaction Conditions | 4µM; 0, 24, 48h |
Applications | Nilotinib inhibits CD8+ T lymphocyte proliferation, even when added 48h after the start of culture, it can inhibit the proliferation of CD8+ T lymphocytes stimulated by PHA/IL-2. |
| Animal experiment [2]: | |
Animal models | BALB/cSlc-nu/nu mice |
Preparation Method | Tumor tissue fragments (5mm3) were transplanted s.c. into the backs of BALB/cSlc-nu/nu mice that were randomized into 3 groups (n = 6-8). Doses of 40mg/kg/day of Imatinib, Nilotinib or pure water (control) were administered by oral gavage daily for 28 days. Tumor size was measured every two to three days. |
Dosage form | 40mg/kg/day for 28 days; p.o. |
Applications | Nilotinib inhibited tumor growth by 69.6%, 85.3% and 47.5% in GK1X, GK2X and GK3X xenograft lines, respectively. |
References: | |
| Cas No. | 641571-10-0 | SDF | |
| المرادفات | AMN107 | ||
| Chemical Name | 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide | ||
| Canonical SMILES | CC1=C(C=C(C=C1)C(=O)NC2=CC(=CC(=C2)N3C=C(N=C3)C)C(F)(F)F)NC4=NC=CC(=N4)C5=CN=CC=C5 | ||
| Formula | C28H22F3N7O | M.Wt | 529.53 |
| الذوبان | ≥ 26.5mg/mL in DMSO, ≥ 5mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8885 mL | 9.4423 mL | 18.8847 mL |
| 5 mM | 0.3777 mL | 1.8885 mL | 3.7769 mL |
| 10 mM | 0.1888 mL | 0.9442 mL | 1.8885 mL |
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