Home Tools
Log in
Cart

Nilotinib

Catalog No. T1524   CAS 641571-10-0
Synonyms: Tasigna, AMN107

Nilotinib (AMN107) is a second-generation Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity.

All products from TargetMol are for Research Use Only. Not for Human or Veterinary or Therapeutic Use.
Nilotinib Chemical Structure
Nilotinib, CAS 641571-10-0
Pack Size Availability Price/USD Quantity
50 mg In stock $ 35.00
100 mg In stock $ 42.00
200 mg In stock $ 50.00
1 mL * 10 mM (in DMSO) In stock $ 50.00
Bulk Inquiry
Get quote
Select Batch  
Purity: 99.83%
Purity: 99.61%
Contact us for more batch information
Biological Description
Chemical Properties
Storage & Solubility Information
Description Nilotinib (AMN107) is a second-generation Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity.
Targets&IC50 Abl (WT):15 nM (cell free)
In vitro Nilotinib (AMN107) inhibited Abl-catalyzed peptide substrate phosphorylation with ~20-fold higher potency than imatinib (IC50: 15 versus 280 nmol/L). AMN107 inhibited the growth of cells expressing wild-type Bcr-Abl with 20-fold higher potency than imatinib (IC50: 13 versus 260 nmol/L) [1].Parent and imatinib-resistant GIST cell lines showed sensitivity to nilotinib in a concentration-dependent manner with the IC50 values of parent GIST cell lines being 3.15±0.31 μM for GK1C and 3.32±0.18 μM for GK3C (n.s.), and the imatinib-resistant cell lines showing IC50 values of 4.10±0.46 μM and 3.96±0.19 μM for GK1C-IR and GK3C-IR (n.s.), respectively [2]. Nilotinib inhibited proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induced apoptosis of HSCs. Nilotinib also induced cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1 [3].
In vivo The percentage of tumor growth inhibition (TGI) was 69.6% for nilotinib in the GK1X xenograft line. In the GK2X xenograft line, TGI was 85.3% for nilotinib [2]. Imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1β and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of TGF-β1 and PDGFR-β [4].
Kinase Assay Kinase assays using wild-type and mutant glutathione S-transferase (GST)–Abl fusion proteins (c-Abl amino acids 220-498) were done as described, with minor alterations. GST-Abl fusion proteins were released from glutathione-Sepharose beads before use; the concentration of ATP was 5 μmol/L. Immediately before use in kinase autophosphorylation and in vitro peptide substrate phosphorylation assays, GST-Abl kinase domain fusion proteins were treated with LAR tyrosine phosphatase according to the manufacturer's instructions. After 1-hour incubation at 30°C, LAR phosphatase was inactivated by addition of sodium vanadate (1 mmol/L). Immunoblot analysis comparing untreated GST-Abl kinase to dephosphorylated GST-Abl kinase was routinely done using phosphotyrosine-specific antibody 4G10 to confirm complete (>95%) dephosphorylation of tyrosine residues and c-Abl antibody CST 2862 to confirm equal loading of GST-Abl kinase. The inhibitor concentration ranges for IC50 determinations were 0 to 5,000 nmol/L (imatinib and AMN107) or 0 to 32 nmol/L (BMS-354825). The BMS-354825 concentration range was extended to 1,000 nmol/L for mutant T315I. These same inhibitor concentrations were used for the in vitro peptide substrate phosphorylation assays. The three inhibitors were tested over these same concentration ranges against GST-Src kinase and GST-Lyn kinase [1].
Cell Research Ba/F3 cell lines were plated in triplicate and incubated with escalating concentrations of imatinib, AMN107, or BMS-354825 for 72 hours. Proliferation was measured using a methanethiosulfonate-based viability assay. IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges for IC50 and IC90 determinations were 0 to 2,000 nmol/L (imatinib and AMN107) or 0 to 32 nmol/L (BMS-354825). The imatinib concentration range was extended to 6,400 nmol/L for mutants with IC50 >2,000 nmol/L. The BMS-354825 concentration range was extended to 200 nmol/L for mutant T315I [1].
Animal Research The GIST xenograft lines GK1X, GK2X and GK3X in nude mice were established from GIST patients as described in our previous study [10]. These xenograft lines were maintained by continual passage in BALB/cSLc-nu/nu mice. Mice bearing GK1X, GK2X and GK3X tumors (6–8 mice per group) were treated daily with vehicle or 40 mg/kg imatinib or nilotinib for 4 weeks. Tumor volume (TV) was determined from caliper measurements of tumor length (L) and width (w) according to the formula LW2/2. TV was determined every two to three days and on the day of evaluation. Mice were sacrificed and the percentage of tumor growth inhibition (TGI) was calculated as follows: TGI (%) ?=? [1– (mean of treatment group tumor volume on evaluation day – mean of treatment group tumor volume on day 1)/(mean of control group tumor volume on evaluation day – mean of control group tumor volume on day 1)]×100 [2].
Synonyms Tasigna, AMN107
Molecular Weight 529.52
Formula C28H22F3N7O
CAS No. 641571-10-0

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

H2O: < 1 mg/mL (insoluble or slightly soluble)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 26 mg/mL (49.1 mM)

TargetMolReferences and Literature

1. O'Hare T, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5. 2. Sako H, et al. Antitumor effect of the tyrosine kinase inhibitor Nilotinib on gastrointestinal stromal tumor (GIST) and Imatinib-resistant GIST cells. PLoS One. 2014 Sep 15;9(9):e107613. 3. Liu Y, et al. Inhibition of PDGF, TGF-β, and Abl signaling and reduction of liver fibrosis by the small molecule Bcr-Abl tyrosine kinase antagonist Nilotinib. J Hepatol. 2011 Sep;55(3):612-625. 4. Rhee CK, et al. Effect of nilotinib on bleomycin-induced acute lung injury and pulmonary fibrosis in mice. Respiration. 2011;82(3):273-87. 6. Fujita KI, et al. Involvement of the Transporters P-Glycoprotein and Breast Cancer Resistance Protein in Dermal Distribution of the Multikinase Inhibitor Regorafenib and Its Active Metabolites. J Pharm Sci. 2017 Sep;106(9):2632-2641. 7. Sun R, Bao M Y, Long X, et al. Metabolic gene NR4A1 as a potential therapeutic target for non‐smoking female non‐small cell lung cancer patients[J]. Thoracic cancer. 2019 Apr;10(4):715-727. 8. Kuang Y, Chai Y, Xu L, et al. Glabrone as a specific UGT1A9 probe substrate and its application in discovering the inhibitor glycycoumarin[J]. European Journal of Pharmaceutical Sciences. 2021: 105786.

TargetMolCitations

1. Cheng S, Jin P, Li H, et al. Evaluation of CML TKI Induced Cardiovascular Toxicity and Development of Potential Rescue Strategies in a Zebrafish Model. Frontiers in Pharmacology. 2021: 2866. 2. Kuang Y, Chai Y, Xu L, et al. Glabrone as a specific UGT1A9 probe substrate and its application in discovering the inhibitor glycycoumarin. European Journal of Pharmaceutical Sciences. 2021: 105786. 3. Sun R, Bao M Y, Long X, et al. Metabolic gene NR4A1 as a potential therapeutic target for non‐smoking female non‐small cell lung cancer patients. Thoracic Cancer. 2019 Apr;10(4):715-727 4. Yan H, Wu W, Hu Y, et al.Regorafenib inhibits EphA2 phosphorylation and leads to liver damage via the ERK/MDM2/p53 axis.Nature Communications.2023, 14(1): 2756. 5. Liu T, Yue X, Chen X, et al.Nilotinib in combination with sunitinib renders MCL-1 for degradation and activates autophagy that overcomes sunitinib resistance in renal cell carcinoma.Cellular Oncology.2024: 1-18.

Related compound libraries

This product is contained In the following compound libraries:
Tyrosine Kinase Inhibitor Library Anti-Cancer Drug Library Anti-Cancer Approved Drug Library Anti-Cancer Active Compound Library Anti-Cancer Clinical Compound Library FDA-Approved & Pharmacopeia Drug Library Drug-induced Liver Injury (DILI) Compound Library Clinical Compound Library FDA-Approved Drug Library Anti-Cancer Metabolism Compound Library

Related Products

Related compounds with same targets
Olverembatinib Cenisertib AG957 Flumatinib mesylate Berbamine dihydrochloride Silybin B CHMFL-ABL-039 Masitinib

TargetMolDose Conversion

You can also refer to dose conversion for different animals. More

TargetMol In vivo Formulation Calculator (Clear solution)

Step One: Enter information below
Dosage
mg/kg
Average weight of animals
g
Dosing volume per animal
ul
Number of animals
Step Two: Enter the in vivo formulation
% DMSO
%
% Tween 80
% ddH2O
Calculate Reset

TargetMolCalculator

Molarity Calculator
Dilution Calculator
Reconstitution Calculation
Molecular Weight Calculator
=
X
X

Molarity Calculator allows you to calculate the

  • Mass of a compound required to prepare a solution of known volume and concentration
  • Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Concentration of a solution resulting from a known mass of compound in a specific volume
See Example

An example of a molarity calculation using the molarity calculator
What is the mass of compound required to make a 10 mM stock solution in 10 ml of water given that the molecular weight of the compound is 197.13 g/mol?
Enter 197.13 into the Molecular Weight (MW) box
Enter 10 into the Concentration box and select the correct unit (millimolar)
Enter 10 into the Volume box and select the correct unit (milliliter)
Press calculate
The answer of 19.713 mg appears in the Mass box

X
=
X

Calculator the dilution required to prepare a stock solution

Calculate the dilution required to prepare a stock solution
The dilution calculator is a useful tool which allows you to calculate how to dilute a stock solution of known concentration. Enter C1, C2 & V2 to calculate V1.

See Example

An example of a dilution calculation using the Tocris dilution calculator
What volume of a given 10 mM stock solution is required to make 20ml of a 50 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=50 μM, V2=20 ml and V1 is the unknown:
Enter 10 into the Concentration (start) box and select the correct unit (millimolar)
Enter 50 into the Concentration (final) box and select the correct unit (micromolar)
Enter 20 into the Volume (final) box and select the correct unit (milliliter)
Press calculate
The answer of 100 microliter (0.1 ml) appears in the Volume (start) box

=
/

Calculate the volume of solvent required to reconstitute your vial.

The reconstitution calculator allows you to quickly calculate the volume of a reagent to reconstitute your vial.
Simply enter the mass of reagent and the target concentration and the calculator will determine the rest.

g/mol

Enter the chemical formula of a compound to calculate its molar mass and elemental composition

Tip: Chemical formula is case sensitive: C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed n the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

bottom

Tech Support

Please see Inhibitor Handling Instructions for more frequently ask questions. Topics include: how to prepare stock solutions, how to store products, and cautions on cell-based assays & animal experiments, etc.

Keywords

Nilotinib 641571-10-0 Angiogenesis Autophagy Cytoskeletal Signaling Tyrosine Kinase/Adaptors Bcr-Abl antitumor AMN-107 AMN 107 tyrosine kinase Inhibitor Tasigna inhibit AMN107 inhibitor

 

TargetMol