| Size | Price | Stock | Qty |
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| 25mg |
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| 250mg |
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| 500mg |
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Purity: =99.87%
Nilotinib HCl hydrate (formerly also known as AMN-107, AMN107 HCl hydrate) is a potent, orally bioavailable aminopyrimidine-derivative Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. It is a medication that has FDA approval for the treatment of chronic myelogenous leukemia that is imatinib resistant. Nilotinib, which was created using imatinib's structural blueprint, outperformed imatinib in the treatment of chronic myelogenous leukemia (CML) that had just been identified or was imatinib-resistant. For wild-type BCR-ABL, it was more effective than imatinib in a variety of CML-derived and transfected cell lines. Additionally effective against gastrointestinal stromal tumors was nilotinib.
| Targets |
Bcr-Abl (IC50 = 30 nM); AMPK
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
The novel, selective Abl inhibitor, Nilotinib (AMN107), is designed to interact with the ATP-binding site of BCR-ABL with a higher affinity than Imatinib. In addition to being significantly more potent compared with Imatinib (IC50<30 nM), Nilotinib also maintains activity against most of the BCR-ABL point mutants that confer Imatinib resistance.
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| Cell Assay |
Human primary Schwann and schwannoma cells are seeded on precoated 96-well plates. Nilotinib is added 40 minutes before stimulation with 100 ng/mL PDGF-DD, and cells are cultured for 72 hours (3 days). Because the half-life of Nilotinib is 18 hours, one-half of the originally added concentrations are added freshly every day. In addition to DAPI staining and determination of the total cell number, the more sensitive and accurate BrdU incorporation method is used to detect proliferating cells. Total cell amount (DAPI) and number of dividing cells (BrdU-positive) are blindly counted using an inverted fluorescent microscope and 200 × magnification. All cells in every well are counted. The total cell number per well differed between various cell batches and is 100–300 cells/well.
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| Animal Protocol |
BALB/cSLc-nu/nu mice with GIST xenograft (GK1X, GK2X and GK3X)[2]
40 mg/kg Oral gavage; daily; 4 weeks |
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| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation While the levels of nilotinib in breast milk appear to be low, and one breastfed infant experienced no adverse reactions while the mother was taking nilotinib, long-term data are currently unavailable. Because nilotinib binds to plasma proteins at a rate as high as 98%, the levels in breast milk are likely low. However, there are few reports of experience with nilotinib use during lactation, so alternative medications may be preferred, especially when breastfeeding newborns or premature infants. The National Comprehensive Cancer Network (NCCN) guidelines recommend avoiding breastfeeding during nilotinib treatment, and the manufacturer recommends discontinuing breastfeeding two weeks after the last dose. ◉ Effects on Breastfed Infants A woman with chronic myeloid leukemia continued taking nilotinib (dosage not specified) for the first 20 months of pregnancy, throughout pregnancy, and during lactation (duration of lactation not specified). No adverse reactions were reported in her breastfed infant. ◉ Impact on breastfeeding and breast milk As of the revision date, no relevant published information was found. |
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| References |
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| Additional Infomation |
Nilotinib hydrochloride monohydrate is the monohydrate-hydrochloride form of nilotinib. Nilotinib is an orally bioavailable aminopyrimidine derivative belonging to the Bcr-Abl tyrosine kinase inhibitor class and possessing antitumor activity. Nilotinib is designed to overcome imatinib resistance caused by Bcr-Abl kinase mutations. After administration, nilotinib binds to the kinase domain of the Abl portion of the Bcr-Abl fusion protein and stabilizes its inactive conformation, thereby inhibiting the constitutive kinase activity of the Bcr-Abl protein. This inhibits Bcr-Abl-mediated proliferation of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) cells. Nilotinib can also inhibit other receptor tyrosine kinases such as platelet-derived growth factor receptor (PDGF-R; PDGFR), mast cell/stem cell growth factor receptor Kit (c-Kit), colony-stimulating factor 1 receptor (CSF-1R; CSF1R), and discoid domain receptor 1 (DDR1), but with weaker inhibitory effects.
Drug Indications Tasigna is indicated for the treatment of: newly diagnosed adults and children with chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia (CML), and children with chronic-phase Philadelphia chromosome-positive CML who are resistant to or intolerant of prior treatments, including imatinib. Tasigna is indicated for the treatment of: newly diagnosed adults and children with chronic-phase Philadelphia chromosome-positive chronic myeloid leukemia (CML); adults with chronic-phase and accelerated-phase Philadelphia chromosome-positive CML who are resistant to or intolerant of prior treatments (including imatinib). There are no efficacy data for patients with blast crisis CML; and children with chronic-phase Philadelphia chromosome-positive CML who are resistant to or intolerant of prior treatments (including imatinib). |
| Molecular Formula |
C28H25CLF3N7O2
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|---|---|
| Molecular Weight |
584.0
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| Exact Mass |
583.171
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| Elemental Analysis |
C, 57.59; H, 4.32; Cl, 6.07; F, 9.76; N, 16.79; O, 5.48
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| CAS # |
923288-90-8
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| Related CAS # |
Nilotinib;641571-10-0;Nilotinib hydrochloride;923288-95-3; Nilotinib monohydrochloride monohydrate;923288-90-8;Nilotinib-d6;1268356-17-7;Nilotinib-d3;1215678-43-5;Nilotinib hydrochloride;923288-95-3; 641571-10-0; 923289-71-8 (hydrochloride dihydrate); 1277165-20-4 (dihydrochloride dihydrate)
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| PubChem CID |
16757572
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| Appearance |
White to off-white solid powder
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| LogP |
6.812
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
41
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| Complexity |
817
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C(C1C=C(NC2N=C(C3C=CC=NC=3)C=CN=2)C(C)=CC=1)NC1C=C(C(F)(F)F)C=C(N2C=C(C)N=C2)C=1.O
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| InChi Key |
YCBPQSYLYYBPDW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H22F3N7O.ClH.H2O/c1-17-5-6-19(10-25(17)37-27-33-9-7-24(36-27)20-4-3-8-32-14-20)26(39)35-22-11-21(28(29,30)31)12-23(13-22)38-15-18(2)34-16-38;;/h3-16H,1-2H3,(H,35,39)(H,33,36,37);1H;1H2
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| Chemical Name |
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide;hydrate;hydrochloride
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| Synonyms |
Nilotinib; AMN 107; AMN107; AMN-107; US brand name: Tasigna. Nilotinib HCl hydrate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 33 mg/mL (~56.51 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7123 mL | 8.5616 mL | 17.1233 mL | |
| 5 mM | 0.3425 mL | 1.7123 mL | 3.4247 mL | |
| 10 mM | 0.1712 mL | 0.8562 mL | 1.7123 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03654768 | Active Recruiting |
Drug: Nilotinib Drug: Dasatinib Drug: Bosutinib |
Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive |
SWOG Cancer Research Network | October 24, 2018 | Phase 2 |
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