Nilotinib (AMN-107)

Catalog No.S1033

For research use only.

Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.

Nilotinib (AMN-107) Chemical Structure

CAS No. 641571-10-0

Selleck's Nilotinib (AMN-107) has been cited by 122 publications

Purity & Quality Control

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Biological Activity

Description Nilotinib (AMN-107) is a selective Bcr-Abl inhibitor with IC50 less than 30 nM in Murine myeloid progenitor cells. Nilotinib induces autophagy through AMPK activition.
Features A selective inhibitor of native and mutant Bcr-Abl.
Targets
Bcr-Abl [1]
(Murine myeloid progenitor cells)
<30 nM
In vitro

Nilotinib inhibits proliferation, migration, and actin filament formation, as well as the expression of α-SMA and collagen in activated HSCs. Nilotinib induces apoptosis of HSCs, which is correlated with reduced bcl-2 expression, increases p53 expression, cleavage of PARP, as well as increases expression of PPARγ and TRAIL-R. Nilotinib also induces cell cycle arrest, accompanied by increased expression of p27 and downregulation of cyclin D1. Interestingly, Nilotinib not only inhibits activation of PDGFR, but also TGFRII through Src. Nilotinib significantly inhibits PDGF and TGFβ-simulated phosphorylation of ERK and Akt. Furthermore, PDGF- and TGFβ-activated phosphorylated form(s) of Abl in human HSCs are inhibited by Nilotinib. [2] Nilotinib inhibits most imatinib-resistant Bcr-Abl mutations, except for T315I. [3] Nilotinib inhibits PDGF-DD-mediated ERK1/2 activation, basal and PDGF-DD-mediated activation of PDGFRβ and Akt, and schwannoma proliferation. Nilotinib is more potent than imatinib, exerting its maximal inhibitory effect at concentrations lower than steady-state trough plasma levels. [4] Nilotinib also significantly reduces the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Nilotinib treatment also significantly inhibits the PDGF-induced proliferation of lung fibroblasts. [5] Nilotinib inhibits the proliferation of Ba/F3 cells expressing p210- and p190-Bcr-Abl, or K562 and Ku-812F cells with IC50 values ≤12 nM. [6]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
EoL-1-cell MkDaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zGc2lEPTB;MD6wNFAyPDRizszN NE\5TlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTV6NkOvK|5USU6JRWK8M4E,
KU812 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV;JR|UxRTBwMECyOFgh|ryP NVLSbJpkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjV3OE[zM{c,W0GQR1XSQE9iRg>?
EM-2 NYj1TW1sT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoDMTWM2OD1yLkCwOFEh|ryP NIDteJE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTV6NkOvK|5USU6JRWK8M4E,
LAMA-84 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRTBwMEC0PUDPxE1? M3fqT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2PTh4Mz:nQnNCVkeHUkyvZV4>
MEG-01 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVXJR|UxRTBwMEC4Nlgh|ryP NGXm[pE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTV6NkOvK|5USU6JRWK8M4E,
BV-173 NE\SfYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHrZOWhKSzVyPUCuNFExQDlizszN MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVU5PjNxJ{7TRW5ITVJ:L3G+
KASUMI-1 NHjyUnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnCb|VjUUN3ME2wMlAzPDF|IN88US=> NELOfFk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTV6NkOvK|5USU6JRWK8M4E,
NB7 NXu1RoxuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7UdnBKSzVyPUCuNVM1OzlizszN M{PWPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2PTh4Mz:nQnNCVkeHUkyvZV4>
BHT-101 M1vKRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXzTPYJrUUN3ME2wMlY1OjZ|IN88US=> MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVU5PjNxJ{7TRW5ITVJ:L3G+
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ACN MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NU[0eJZ5UUN3ME2xMlU2ODd5IN88US=> NXrXfoU6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjV3OE[zM{c,W0GQR1XSQE9iRg>?
A204 NFyyd4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXm3VIJiUUN3ME2xMlU4OjB3IN88US=> MmS4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNlU2QDZ|Lze+V2FPT0WUPD;hQi=>
HOP-62 M2XkdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml7tTWM2OD1zLkiyNFc4KM7:TR?= M2LwNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2PTh4Mz:nQnNCVkeHUkyvZV4>
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HCC1806 MkjlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTNSJpHUUN3ME2yMlc1OzJ5IN88US=> MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVU5PjNxJ{7TRW5ITVJ:L3G+
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RS4-11 MojaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DJRmlEPTB;Mj65NFYzOyEQvF2= NEDRRnE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTV6NkOvK|5USU6JRWK8M4E,
JAR NGHNOZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXnJR|UxRTJwOUKwPFQh|ryP NWfwd|lyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOjV3OE[zM{c,W0GQR1XSQE9iRg>?
T98G Ml;XS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWDxfVVIUUN3ME2zMlAyOzF|IN88US=> MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVU5PjNxJ{7TRW5ITVJ:L3G+
NCI-SNU-1 NVzrPYRzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUXJR|UxRTNwNECwPVIh|ryP MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVU5PjNxJ{7TRW5ITVJ:L3G+
SK-MEL-1 MoHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrH[HpxUUN3ME2zMlQ{ODJ7IN88US=> M1fLRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFI2PTh4Mz:nQnNCVkeHUkyvZV4>
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HT-1080 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnzhTWM2OD1|LkmxO|c2KM7:TR?= MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVU5PjNxJ{7TRW5ITVJ:L3G+
G-402 MlvsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHf4ZZBKSzVyPUSuN|EzODNizszN MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyyOVU5PjNxJ{7TRW5ITVJ:L3G+
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HAL-01 MkiwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkfUTWM2OD12Lki4NlQzKM7:TR?= NFXsbnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwzPTV6NkOvK|5USU6JRWK8M4E,
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OHS-50 MU\xTHRUKGG|c3H5 MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDPTHMuPTBiY3XscJM> NEnMXGs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SK-N-SH MV\xTHRUKGG|c3H5 NVn3XotqeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW0tvTj3TTEBk\Wyucx?= MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Assay
Methods Test Index PMID
Western blot p-AMPKα / AMPKα / p-AMPKβ1 / AMPKγ2 / p-LKB1 / LKB1 / CaMKIIβ ; DNMT1 / DNMT3a / DNMT3b ; pABL1 / p-NF-κB1 / NF-κB / STAT3 / p-STAT3 / IL-1β / IL-6 / COX2 23677989 28720666 31396300
Growth inhibition assay Cell viability 23677989
In vivo Nilotinib reduces collagen deposition and α-SMA expression in CCl4 and BDL-induced fibrosis. Nilotinib could induce HSC undergoing apoptosis, which is correlated with downregulation of bcl-2. [2] Nilotinib attenuates the extent of lung injury and fibrosis. Nilotinib therapy significantly reduces the levels of hydroxyproline on days 14 and 21, which is accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFRβ. [5] AMN107 prolongs survival of mice injected with Bcr-Abl-transformed hematopoietic cell lines or primary marrow cells, and prolongs survival in imatinib-resistant CML mouse models. [6]

Protocol (from reference)

Cell Research:[4]
  • Cell lines: Human primary Schwann and schwannoma cells
  • Concentrations: 1-10 μM
  • Incubation Time: 72 hours
  • Method: 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.
Animal Research:[6]
  • Animal Models: Systemic 32D Bcr-Abl leukemia model in Female BALB/c mice, Bioluminescent Bcr-Abl model of CML in Female NOD-SCID mice and Bone marrow transplant Bcr-Abl model of CML in syngeneic Balb/c recipient mice
  • Dosages: 75 mg/kg, 100 mg/kg
  • Administration: Oral administration

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
4% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

3mg/mL

Chemical Information

Molecular Weight 529.52
Formula

C28H22F3N7O

CAS No. 641571-10-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=C(C=C(C=C1)C(=O)NC2=CC(=CC(=C2)C(F)(F)F)N3C=C(N=C3)C)NC4=NC=CC(=N4)C5=CN=CC=C5

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05185947 Not yet recruiting Drug: Paclitaxel|Drug: Nilotinib Peritoneal Carcinomatosis|Peritoneal Neoplasms|Ovarian Cancer|Ovarian Neoplasms|Colorectal Cancer|Colorectal Neoplasms|Appendiceal Cancer|Appendiceal Neoplasms National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) January 18 2022 Phase 2
NCT04326933 Not yet recruiting Drug: Tyrosine kinase Inhibitors (Imatinib & Nilotinib) Patients Diagnosed as Chronic Meyloid Leukemia Assiut University October 20 2020 --
NCT04002674 Recruiting Drug: Placebo oral capsule|Drug: Nilotinib Oral Capsule Dementia With Lewy Bodies Georgetown University|National Institutes of Health (NIH) January 10 2020 Phase 2
NCT03942094 Recruiting Drug: Nilotinib Chronic Myeloid Leukemia Chronic Phase|Nilotinib Shenzhen Second People''s Hospital|Zhongshan City People''s Hospital|Affiliated Hospital of Guangdong Medical University|Huazhong University of Science and Technology Union Shenzhen Hospital|Dongguan People''s Hospital|Longgang District Central Hospital of Shenzhen June 1 2019 Phase 3

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
I would like to use AMN-107 for in vivo studies in mice, can you give me some suggestions about the in vivo formulation?

Answer:
For in vivo study, we recommend to use 4% DMSO+30% PEG 300+5% Tween 80+ddH2O up to 3mg/ml.

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