Nilotinib

別名：AMN-107

製品コード：S1033 純度：99.89%

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

CAS No. 641571-10-0

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
25mg	JPY 22000	国内在庫あり
100mg	JPY 44500	国内在庫あり
1g	JPY 145500	国内在庫あり

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文献中Selleckの製品使用例（149）

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製品安全説明書

現在のバッチを見る：純度： 99.89%

99.89

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シグナル伝達経路

Bcr-Ablシグナル伝達経路

Bcr-Abl阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
BA/F3	Antitumor assay	75 mg/kg	19 days	Antitumor activity against mouse BA/F3 cells expressing wild type Bcr-Abl xenografted in CB17 SCID mouse assessed as median survival time at 75 mg/kg, po administered on day 3 once daily for 19 days relative to control	19572547
BA/F3	Antitumor assay	75 mg/kg	19 days	Antitumor activity against mouse BA/F3 cells expressing wild type Bcr-Abl xenografted in CB17 SCID mouse assessed as increase in mouse survival at 75 mg/kg, po administered on day 3 once daily for 19 days relative to control	19572547
vascular smooth muscle cells	Antiangiogenic assay	0.15 uM	72 hrs	Antiangiogenic activity in HUVEC co-cultured with vascular smooth muscle cells assessed as inhibition of cell growth at 0.15 uM after 72 hrs	22853993
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生物活性

製品説明

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

特性

A selective inhibitor of native and mutant Bcr-Abl.

Targets

Bcr-Abl ^[1]
(Murine myeloid progenitor cells)

<30 nM

In Vitro
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]
細胞実験	細胞株	Human primary Schwann and schwannoma cells
	濃度	1-10 μM
	反応時間	72 hours
	実験の流れ	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.
実験結果図	Methods	Biomarkers	結果図	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
	Growth inhibition assay	Cell viability		23677989

In Vivo
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]
動物実験	動物モデル	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
	投与量	75 mg/kg, 100 mg/kg
	投与経路	Oral administration

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT06409936	Not yet recruiting	CML Chronic Phase\|Chronic Myeloid Leukemia Chronic Phase\|Chronic Myeloid Leukemia BCR/ABL-Positive\|Chronic Myeloid Leukemia	Gruppo Italiano Malattie EMatologiche dell''Adulto\|Fundacion Espanola para la Curacion de la Leucemia Mieloide Cronica	September 2024	Phase 2
NCT05185947	Recruiting	Gynecologic Cancer\|Gynecologic Neoplasms\|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)	October 13 2022	Phase 2
NCT04326933	Unknown status	Patients Diagnosed as Chronic Meyloid Leukemia	Assiut University	January 1 2020	--
NCT04002674	Recruiting	Dementia With Lewy Bodies	Georgetown University\|National Institutes of Health (NIH)	July 1 2019	Phase 2

参考
[1] Weisberg E, et al. Blood. 2007, 109(5), 2112-2120. [2] Liu Y, et al. J Hepatol. 2011, 55(3), 612-625. [3] Hochhaus A, et al. Cell Cycle. 2011, 10(2), 250-260. [4] Ammoun S, et al. Neuro Oncol. 2011, 13(7), 759-766. [5] Rhee CK, et al. Respiration. 2011, 82(3), 273-287. [6] Weisberg E, et al. Cancer Cell. 2005, 7(2), 129-141. + 展開

参考

+ 展開

化学情報

分子量	529.52	化学式	C₂₈H₂₂F₃N₇O
CAS No.	641571-10-0	SDF	Download Nilotinib SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	１ケ月-20°Cin solvent

In vitro
Batch:

DMSO : 35 mg/mL ( (66.09 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

Clear solution

2%DMSO 1 40%PEG300 Click to order 2 5%Tween 80 Click to order 3 53%ddH2O

2.0mg/ml (3.78mM)

Taking the 1 mL working solution as an example, add 20 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 530 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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よくある質問（FAQ）

質問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?

回答
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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C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
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