Nilotinib(AMN-107)
Nilotinib (AMN-107; CAS 641571-10-0) is an orally bioavailable, selective inhibitor targeting the BCR-ABL tyrosine kinase. Derived structurally from imatinib, nilotinib inhibits both wild-type (WT p210) and mutant forms (E281K, E292K, F317L, M351T, F486S) of BCR-ABL, reducing their autophosphorylation activity with IC50 values ranging from 20 to 42 nM. It also exhibits substantial inhibitory activity against activated KIT mutants (e.g., V560del, K642E) and various KIT double mutations, and effectively suppresses PDGFRα and PDGFRβ kinases. Nilotinib is utilized extensively in research related to chronic myeloid leukemia and gastrointestinal stromal tumors involving kinase-driven pathologies.
References:
[1] Weisberg E, Manley P, Mestan J, et al. AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. British Journal of Cancer, 2006, 94(12): 1765-1769.
[2] Blay J Y, Von Mehren M. Nilotinib: a novel, selective tyrosine kinase inhibitor//Seminars in oncology. WB Saunders, 2011, 38: S3-S9.
- 1. Patrick J Nugent, Heungwon Park, et al. "Decoding post - transcriptional regulatory networks by RNA - linked CRISPR screening in human cells." Nat Methods. 2025 Jun;22(6):1237-1246 PMID: 40442371
- 2. Emily J Stadnicki, Hannes Ludewig, et al. "Dual-Action Kinase Inhibitors Influence p38α MAP Kinase Dephosphorylation." bioRxiv. 2024 Aug 8:2024.05.15.594272 PMID: 39149408
- 3. Haiyan Dong, Chuangyu Wen, et al. "Nilotinib boosts the efficacy of anti-PDL1 therapy in colorectal cancer by restoring the expression of MHC-I." J Transl Med. 2024 Aug 14;22(1):769 PMID: 39143573
- 4. Seung-Hwan Kwon, Sangjune Kim, et al. "A Novel, Selective c-Abl Inhibitor, Compound 5, Prevents Neurodegeneration in Parkinson's Disease." J Med Chem. 2021 Oct 28;64(20):15091-15110. PMID: 34583507
- 5. Saebom Lee ,Sangjune Kim ,et al."The c-Abl inhibitor, Radotinib HCl is neuroprotective in a preclinical Parkinson’s disease mouse model." Human Molecular Genetics, ddy143.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 529.53 |
| Cas No. | 641571-10-0 |
| Formula | C28H22F3N7O |
| Synonyms | AMN-107; Tasigna; AMN107 |
| Solubility | ≥26.5 mg/mL in DMSO; insoluble in H2O; ≥5 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
CD34+ cells from individual patients with CML |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
5 μM, 16 hours |
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Applications |
After 16 hours in culture with nilotinib, long enough for inhibition of CrkL phosphorylation but not for induction of apoptosis, the total CD34+ cell samples studied exhibited only partial and variable inhibition (range, 49% to 0% inhibition) of CrkL phosphorylation. |
| Animal experiment: [2] | |
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Animal models |
C57Bl/6J mice injected with 8093 lymphoma cells |
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Dosage form |
Oral administration, 75 mg/kg, daily |
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Applications |
Vehicle treated mice became moribund within 3 weeks of the transplantation. They showed clear symptoms of ALL. Nilotinib-treated mice lived statistically significantly longer as compared with the vehicle-treated mice. This result clearly indicated that nilotinib was very effective in inhibiting the proliferation of the leukemic cells in vivo. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] 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. Blood, 2007, 109(9): 4016-4019. [2] Kaur P, Feldhahn N, Zhang B, et al. Nilotinib treatment in mouse models of P190 Bcr/Abl lymphoblastic leukemia. Mol Cancer, 2007, 6(10): 67-77. |
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| Description | Nilotinib (AMN-107) is an inhibitor of Bcr-Abl with IC50 less than 30 nM. | |||||
| Targets | Bcr-Abl | |||||
| IC50 | 30 nM | |||||
Quality Control & MSDS
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