Nilotinib

カタログ番号 T1524 CAS 641571-10-0

別名: Tasigna, AMN107

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

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Nilotinib, CAS 641571-10-0

パッケージサイズ	在庫状況	単価(税別)
サンプルについてお問い合わせ
50 mg	在庫あり	￥ 8,000
100 mg	在庫あり	￥ 10,000
200 mg	在庫あり	￥ 11,500
1 mL * 10 mM (in DMSO)	在庫あり	￥ 11,500

バルクのお問い合わせ

バッチを選択

純度: 99.83%

COA DATASHEET SDS LCMS HNMR HPLC

純度: 99.61%

COA DATASHEET SDS HPLC HNMR

COA DATASHEET SDS HNMR

COA DATASHEET SDS

バッチの詳細情報はお問い合わせください

生物学的特性に関する説明

化学的特性

保存条件 & 溶解度情報

説明	Nilotinib (AMN107) is a second-generation Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity.
ターゲット＆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].
キナーゼ試験	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].
細胞研究	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].
動物実験	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].

別名	Tasigna, AMN107
分子量	529.52
分子式	C28H22F3N7O
CAS No.	641571-10-0

保存条件

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

溶解度情報

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

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

DMSO: 26 mg/mL (49.1 mM)

参考文献

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.

引用文献

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.

投与量変換

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

In vivo投与量計算 (透明溶液)

ステップ1: 以下の情報を入力してください

投与量

mg/kg

動物の平均体重

動物あたりの投与量

動物数

溶媒の組成を入力してください

% DMSO+

% +

% Tween 80+

% ddH₂O

%DMSO+

計算するリセット

計算結果:

作業濃度: mg/ml;

DMSO溶液の作成方法: mg あらかじめ溶解した薬剤 μL DMSO (マスター溶液の濃度 mg/mL)，濃度がそのバッチの薬剤のDMSO溶解度を超える場合は、まずご連絡ください。

生体内薬剤の調合法：取る μL DMSO マスター溶液、次に追加 μL PEG300，確実に混ぜてから加える μL Tween 80，確実に混ぜてから加える μL ddH₂O, 確実に混ぜる

お問合せ内容:

必ず順番通りに溶媒を加えてください。ボルテックスミキサーや超音波、湯煎することで溶解しやすくなります

計算器

モル濃度計算機

希釈計算機

再構成計算

分子量計算機

質量

濃度

体積

分子量

モル度計算機では以下の計算が可能です

既知の体積と濃度の溶液を調製するために必要な化合物の質量
質量が既知の化合物を目的の濃度まで溶解させるのに必要な溶液の量
特定の体積の中に既知の質量の化合物を入れて得られる溶液の濃度

参考例

モル濃度計算機を使用したモル濃度計算の例
化合物の分子量が197.13g/molである場合、10mlの水に10mMのストック溶液を作るのに必要な化合物の質量はどれくらいですか？
［分子量（MW）］の欄に［197.13］と入力してください
[濃度]ボックスに10と入力し、正しい単位（millimolar）を選択します
[容量]ボックスに10と入力し、正しい単位（milliliter）を選択します
計算を押します
答えの19.713mgが質量欄に表示されます

濃度 (開始)

体積 (開始)

濃度 (終了)

体積 (終了)

溶液を作るのに必要な希釈率の計算

溶液の調製に必要な希釈率の算出
希釈計算機は、既知の濃度の原液をどのように希釈するかを計算することができる便利なツールです。V1を計算するためにC1、C2＆V2を入力します。

参考例

Tocrisの希釈計算器を用いた希釈計算の一例
50μMの溶液を20ml作るためには、10mMの原液を何ml必要ですか？
C1V1=C2V2という式を用いて、C1=10mM、C2=50μM、V2=20ml、V1を未知数とします。
濃度（開始）ボックスに10を入力し正しい単位(millimolar)を選択してください
濃度（終了）ボックスに50を入力し正しい単位(millimolar)を選択してください
体積（終了）ボックスに20を入力し正しい単位(millimolar)を選択してください
計算を押します
100 microliter (0.1 ml) という答えが体積（開始）ボックスに表示されます。

分子式

分子量 g/mol

化合物の化学式を入力して、そのモル質量や元素組成を計算します

Tヒント：化学式は大文字と小文字を区別します。: C10H16N2O2 c10h16n2o2

化合物のモル質量（分子量）を計算する手順:
化学物質のモル質量を計算するには、その化学式を入力し、「計算」をクリックしてください。.
分子質量、分子量、モル質量、モル重量の定義:
分子質量（分子量）とは、物質の1分子の質量であり、統一された原子質量単位（u）で表されます。(1uは炭素12の1原子の質量の1/12に等しい）
モル質量（molar weight）とは、ある物質の1モルの質量のことで、単位はg/molです。

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技術サポート

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

本ウェブサイトに掲載されている製品は全て研究用試薬です。研究目的以外の用途にはご使用できません。

Nilotinib

保存条件

溶解度情報

参考文献

引用文献

関連化合物ライブラリー

関連製品

投与量変換

In vivo投与量計算 (透明溶液)

計算器

モル度計算機では以下の計算が可能です

溶液を作るのに必要な希釈率の計算

バイアルを再構成するのに必要な溶媒の量を計算する.

化合物の化学式を入力して、そのモル質量や元素組成を計算します

技術サポート

Keywords