Canertinib (CI-1033)

製品コードS1019 別名:PD183805

Canertinib (CI-1033)化学構造

分子量(MW):485.94

Canertinib (CI-1033)は一種のパン( pan)-ErbB阻害剤で、EGFRとErbB2に作用する時のIC50値が1.5 nMと9.0 nMに分かれることです。Canertinib (CI-1033)はPDGFR、FGFR、InsR、PKCとCDK1/2/4に抑制活性を表しません。臨床3期。

サイズ 価格 在庫  
USD 88 あり
USD 214 あり
USD 340 あり
USD 844 あり

カスタマーフィードバック(7)

  • (B–C) LNCaP (B) and LNCaP-AI (C) cells were transiently transfected with sPLA2-IIa(-800)-Luc (0.5 lg). The cells were then treated with Erlotinib (20 lM), Gefitinib (20 lM), Lapatinib (20 lM), CI-1033 (8 lM), LY294002 (20 lM) and Bortezomib (20 lM) without or with EGF (100 ng/ml) for 24 h. Luciferase assay was performed according to a standard protocol with Renilla luciferase as an internal control. Data are presented as the mean (±SD) of duplicate values of a representative experiment that was independently repeated for five times.

    Carcinogenesis 2010 31, 1948–1955. Canertinib (CI-1033) purchased from Selleck.

    LNCaP-AI cells were starved in 1% stripped medium for 24 h. The cells were then treated with Erlotinib (20 μM), Gefitinib (20 μM), Lapatinib (20 μM), CI-1033 (8 μM), LY294002 (20 μM) and Bortezomib (20 μM) for 24 h. Cell culture medium was collected from each sample and subjected to ELISA for sPLA2-IIa. The condition medium samples were diluted 10 times for ELISA. Average of duplicate samples was converted to nanogram per milliliter against standard curve. The data represent one of five repeated experiments.

     

     

    Carcinogenesis 2010 31, 1948–1955. Canertinib (CI-1033) purchased from Selleck.

  •  

    Involvement of PKC δ in the reactivation of EGFR family members and downstream Akt and Erk signaling following prolonged c-Met TKI treatment. (B) H1993 cells were treated with SU1274 for 4 h (lane 2) or 48 h (lane 3–6). CI-1033 (1.5 μM, lane 4), rottlerin (10 μM, lane 5), or GO6976 (10 μM, lane 6) were added 4 hours before the cells were harvested. Untreated (lane 1) or treated cells were analyzed by immunobloting with the indicated antibodies.

    Cell Cycle 2009 13, 2050-2056. Canertinib (CI-1033) purchased from Selleck.

    Involvement of PKC δ in the reactivation of EGFR family members and downstream Akt and Erk signaling following prolonged c-Met TKI treatment. H1993 cells were incubated continuously with DMSO (◆), CI-1033 (1.5 μM), SU11274 (2.5 μM, ▲), 17-AAG (0.5 μM, *), SU11274 and CI-1033 (□), or SU11274 and rottlerin (1 μM, △). Cell density was monitored for 6 consecutive days by MTS assay. Each point represents the mean of 4 determinations; error bars, SD.

    Cell Cycle 2009 13, 2050-2056. Canertinib (CI-1033) purchased from Selleck.

  • After starved in serum-free medium for 24h, Breast cancer cells incubated with the indicated concentrations of CI-1033 for 3h,followed by 15-minute stimolation of 100ng/ml EGF

     

     

    Dr. Zhang of Tianjin Medical University. Canertinib (CI-1033) purchased from Selleck.

    H1975 cells were pretreated with 10nm EGF for 15 min and then treated with the indicated concentrations of  CI-1033 for 2 hours.

     

     

    Dr. Kian Kani of Cedars-Sinai Medical Center. Canertinib (CI-1033) purchased from Selleck.

  • A431 80% confluent 10cm plates, 24hour FBS starvation,  then treatment with compounds at 10nM for 30mins, followed by 5 minutes of 0.05ug/ml of EGF.  Pellet was sonicated (setting 5, 5 seconds, twice), then quenched with 2XGSB.  Loaded 10ul on AnyKD BioRad gel (20mins at 250V), transfered with BioRad Turbo system for 15 minutes (1.5A, 25V).  Blocked with 5% milk for 1 hour at RT.  Rocked overnight at 1:1000 in 5% BSA with primary Abs; Anti-rabbit secondary Ab at 1:2000 in 5% milk for 1 hour, developed with Thermo Femto Kit.

    Canertinib (CI-1033) purchased from Selleck.

製品安全説明書

EGFR阻害剤の選択性比較

生物活性

製品説明 Canertinib (CI-1033)は一種のパン( pan)-ErbB阻害剤で、EGFRとErbB2に作用する時のIC50値が1.5 nMと9.0 nMに分かれることです。Canertinib (CI-1033)はPDGFR、FGFR、InsR、PKCとCDK1/2/4に抑制活性を表しません。臨床3期。
特性 First kinase inhibitor to show irreversible activity and to have entered clinical trials (serving as a template for further development).
靶点
EGFR [1]
(Cell-free assay)
ErbB2 [1]
(Cell-free assay)
1.5 nM 9.0 nM
In vitro試験

CI-1033 shows excellent potency for irreversible inhibition of erbB2 autophosphorylation in MDA-MB 453 cells. CI-1033 also shows high permeability in Caco-2 cells and inhibits secretory transport of vinblastine, which indicates that CI-1033 is a likely inhibitor of the P-gp. [1] CI-1033 alone, significantly suppresses constitutively activated Akt and MAP kinase. In combination with gemcitabine, CI-1033 inhibits Akt and prevents increased levels of MAPK phosphorylation. CI-1033 stimulates p27 expression and p38 phosphorylation in MDA-MB-453 cells. [2] CI-1033 is highly specific to the erbB receptor family and not sensitive to PGFR, FGFR or IR even at 50 μM. CI-1033 shows high levels of inhibition in A431 cells expressing EGFR with IC50 of 7.4 nM. CI-1033 suppresses heregulin-stimulated tyrosine phosphorylation of erbB2, erbB3 and erbB4 with IC50 of 5, 14 and 10 nM, respectively. CI-1033 also inhibits expression of pp62c-fos in response to heregulin. [3] CI-1033 is predicted to modify Cys773 covalently within the ATP binding site of the HER2 kinase and enhances destruction of both mature and immature ErbB-2 molecules. [4] CI-1033 induces a significant decrease in measurable phosphorylation of tyrosine residues 845 and 1068 of EGFR, which are responsible for Src and Ras/MAPK signaling respectively. The corresponding residues of Her-2, tyrosine residues 877 and 1248 are dephosphorylated significantly by CI-1033 at a concentration of 3 μM or higher. CI could block EGFR internalization and increase the rate of apoptosis in primary osteosarcoma cells in a titratable fashion. [5] In addition, CI-1033 inhibits the proliferation of TT, TE2, TE6 and TE10 cells significantly at 0.1 nM. [6]

In vivo試験 CI-1033 shows impressive activity against A431 xenografts in nude mice at 5 mg/kg of body weight. [1] CI-1033 (20 to 80 mg/kg/d) achieves a high degree of tumor regressions in H125 xenograft models. [3] Oral administration of CI-1033 causes a marked inhibition of growth in TT, TE6 and TE10 xenografts in nude mice, without animal death and <10% weight loss. [6]

プロトコル(参考用のみ)

キナーゼアッセイ:[1]
+ 展開

Tyrosine Kinase Assays:

Enzyme assays for determination of IC50 are performed in 96-well filter plates in a total volume of 0.1 mL, containing 20 mM Hepes, pH 7.4, 50 mM sodium vanadate, 40 mM magnesium chloride, 10 μM adenosine triphosphate (ATP) containing 0.5 mCi of [32P]ATP, 20 mg of polyglutamic acid/tyrosine, 10 ng of EGFR tyrosine kinase, and appropriate dilutions of CI-1033. All components except the ATP are added to the well and the plate is incubated with shaking for 10 min at 25 °C. The reaction is started by adding [32P]ATP, and the plate is incubated at 25 °C for another 10 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid (TCA). The plate is kept at 4 °C for at least 15 min to allow the substrate to precipitate. The wells are then washed five times with 0.2 mL of 10% TCA and 32P incorporation determined with a Wallac β plate counter.
細胞アッセイ: [6]
+ 展開
  • 細胞株: TT, TE2, TE6 and TE10 cells
  • 濃度: 0.1-5.0 nM
  • 反応時間: 1, 3, 5 and 7 days
  • 実験の流れ: Cells (1 × 104) are seeded in each well of a 24-well plastic culture plate and left overnight in DMEM or RPMI-1640 supplemented with 10% FBS. The next morning, the cells are treated with the indicated concentrations of CI-1033 (0.1-5.0 nM) for varying periods (1, 3, 5 and 7 days). After treatment, the cells are counted using a Coulter counter. The percent of cell proliferation is calculated by this formula: treatment cell number/control cell number × 100 for each time period.
    (参考用のみ)
動物実験:[1]
+ 展開
  • 動物モデル: A431 xenografts established in nude mice
  • 製剤: In solution as the isethionate salts
  • 投薬量: ~18 mg/kg
  • 投与方法: Administered orally
    (参考用のみ)

溶解度 (25°C)

体外 Ethanol 9 mg/mL (18.52 mM)
DMSO 2 mg/mL (4.11 mM)
Water <1 mg/mL
体内 30% propylene glycol, 5% Tween 80, 65% D5W 10 mg/mL

* <1 mg/mlは製品が微弱に溶解する或いは溶解しないことを示します。
* 溶解度検測はSelleck技術部門によって行いますので、文献より提供された溶解度と差異がある可能性がありますが、生産工芸と不同ロット(lot)で起きる正常な現象ですから、ご安心ください。

化学情報

分子量 485.94
化学式

C24H25ClFN5O3

CAS No. 267243-28-7
保管
in solvent
別名 PD183805

便利ツール

モル濃度計算器

モル濃度計算器

解決のために必要とされるマス、ボリュームまたは濃度を計算してください。

マス (g) = 濃度 (mol/L) x ボリューム (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • マス
    濃度
    ボリューム
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備することを要求される希釈剤を計算してください. セレック希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 輸入 輸出 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

マス 濃度 ボリューム 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00050830 Completed Lung Neoplasms Pfizer January 2003 Phase 2
NCT00174356 Completed Carcinoma, Non-Small Cell Lung Pfizer December 2002 Phase 1
NCT00051051 Completed Breast Neoplasms Pfizer December 2002 Phase 2

技術サポート

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

Handling Instructions

他の質問がある場合は、お気軽くお問合せください。

  • * 必須

よくある質問(FAQ)

  • 問題1:

    I would like to know which is the best option/solvent to dilute CI-1033 (Catalog No.S1019) for in vivo experiments. (I am treating mice at 30mg/mL of CI-1033.)

  • 回答:

    The compound in the formulation recommended (30% Propylene glycol, 5% Tween 80, 65% D5W) on our product page at 30mg/ml is suspension. It’s fine for oral gavage.

EGFR信号経路図

EGFR Inhibitors with Unique Features

相関EGFR製品

Tags: Canertinib (CI-1033)を買う | Canertinib (CI-1033) ic50 | Canertinib (CI-1033)供給者 | Canertinib (CI-1033)を購入する | Canertinib (CI-1033)費用 | Canertinib (CI-1033)生産者 | オーダーCanertinib (CI-1033) | Canertinib (CI-1033)化学構造 | Canertinib (CI-1033)分子量 | Canertinib (CI-1033)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID