GDC-0879

製品コードS1104 別名:AR-00341677

GDC-0879化学構造

分子量(MW):334.37

GDC-0879は一種の新たで、有効で、選択性的なB-Raf阻害剤で、A375とColo205の細胞の中でIC50値が0.13nMですが、c-Rafも抑制する作用があっても、他のタンパク質キナーゼを抑制する作用がありません。

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JPY 15838.68 あり
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JPY 38876.76 あり
JPY 67674.36 あり

カスタマーフィードバック(5)

  •  

    Melanoma cell viability and in vivo growth by cyclindependent kinase 2/4 inhibition. Western blot analysis for c-Jun, phosphorylated-ERK1/2 (Thr202/Tyr204) (p-ERK1/2), and total ERK1/2 protein levels was done for human melanoma cell lines treated with the BRAFV600E inhibitor GDC-0879 (1 μM), or MEK inhibitors CI-1040 (1 μM), U0126 (1 μM), and PD98059 (10 μM) for 18 hours.

    J Natl Cancer Inst 2012 104(21), 1673-9. GDC-0879 purchased from Selleck.

    Melanoma cell viability and in vivo growth by cyclindependent kinase 2/4 inhibition. In vivo growth of LOXIMVI xenografts in athymic nude Foxn1nu mice is shown. Tumors were allowed to grow to a maximum volume of 250mm3, and the mice were subsequently treated daily at the indicated dose levels with CDK2/4 inhibitors by intraperitoneal injection in combination with a BRAFV600E- or MEK-inhibitor. CDK2/4 inhibitor (CVT-313/indolocarbazole CDK4-I) treatment sensitizes tumors to GDC-0879 and CI1040.

    J Natl Cancer Inst 2012 104(21), 1673-9. GDC-0879 purchased from Selleck.

  • Effect of RAF or multikinase inhibitors on RAF1-proficient and -deficient DIH. Immunoblot analysis of DIH treated with GDC-0879 (GDC), Sorafenib (SOR) or PP2. Proliferation was assessed after a 48 h treatment, and immunoblotting after 1 h treatment. TUBA, loading control.

    Nat Commun, 2016, 7:13781. GDC-0879 purchased from Selleck.

    RAF inhibitors induce dimer formation between KSR and RAF, and activate KSR by CRAF. (A) GDC0879 but not PLX4720 induces BRAF/CRAF dimers. Cells overexpressing myc-CRAF and BRAF were treated with drug for 1 h and CRAF immunoprecipitates were immunoblotted for BRAF and CRAF (epitope tagged with myc). (B) GDC0879 but not PLX4720 enhances KSR/BRAF complexes. KSR immunoprecipitates were prepared from cells overexpressing FLAG-KSR and BRAF after treatment with the indicated drug for 1 h and immunoblotted using antibodies to BRAF. (C) Both GDC0879 and PLX4720 induce KSR/CRAF complexes.KSR immunoprecipitates were prepared from cells overexpressing FLAG-KSR and myc-CRAF after treatment with the indicated drug for 1 h and immunoblotted for CRAF using myc antibodies. (D and E) Requirement of KSR for drug-induced ERK activation. Lysates fromwild-type and KSR deficient fibroblasts, transfected with RASV12, were treated with the indicated doses of either GDC-0879 (D) or PLX4720 (E) for 1 h. Lysates were immunoblotted for phospho-ERK1 and 2, ERK2, and RASV12. (F) KSR and CRAF cooperate to activate MEK. Cells expressing the indicated constructs were treated with a 50 μM PLX4720 for 2 h before cell lysates were prepared and analyzed for pMEK by immunoblotting. CRAF(TM) refers to the T421M gatekeeper mutant that cannot bind to the drug(4). (G) KSR in vitro kinase reactions. Cells were cotransfected with WT or ATP binding deficient KSR and CRAF and immunoprecipitates prepared after cells were treated with an activating dose of PLX (10 μM) for 1 h. KSR immunoprecipitates were prepared, pretreated with 50 μM PLX4720 to inhibit coprecipitating RAF activity, and then tested for kinase activity using purified MEK. MEK phosphorylation was detected using a pMEK specific antibody.

    Proc Natl Acad Sci USA 2011 108, 6067-6072. GDC-0879 purchased from Selleck.

  • B-RafV600E mutated melanoma line, A375, was treated with different doses of GDC0879 for 1 h or 24 h. Cell lysates were analyzed by Western blotting to determine the levels of phosphorylated MEK1/2 (pMEK1/2) and phosphorylated ERK1/2 (pERK1/2).

     

     

    Dr. Jong-in Park from Medical College of Wisconsin. GDC-0879 purchased from Selleck.

製品安全説明書

Raf阻害剤の選択性比較

生物活性

製品説明 GDC-0879は一種の新たで、有効で、選択性的なB-Raf阻害剤で、A375とColo205の細胞の中でIC50値が0.13nMですが、c-Rafも抑制する作用があっても、他のタンパク質キナーゼを抑制する作用がありません。
ターゲット
B-Raf [1]
(A375, Colo205 cells)
0.13 nM
体外試験

GDC-0879 also inhibits cellular pERK with IC50 of 63 nM. GDC-0879 shows comparable potency in A375 melanoma and Colo205 colorectal carcinoma cell lines, both of which are B-RafV600E mutant, with IC50 of 59 nM and 29 nM for pMEK1 inhibition respectively. GDC-0879 potently inhibits B-RafV600E in Malme3M cells with IC50 of 0.75 μM. GDC-0879 also shows EC50 values < 0.5 μM in many tumor cells (A375, 624, SK-MEL-28, Malme3M, C32, 928, 888, G-361, Colo205, Colo206, SW1417, CL34, and Colo201). [1]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human MALME3M cells M1O4c2Z2dmO2aX;uJIF{e2G7 M{PQO2lvcGmkaYTpc44hd2ZiRWLLNU8zKHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBOSUyPRUPNJINmdGy|LDDJR|UxRTBwME[zJO69VQ>? NV3Nco16OTF5MUewNFE>
human A375 cells NUjuSXZMWHKxbHnm[ZJifGmxbjDhd5NigQ>? NHnTeY9CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFGzO|Uh[2WubIOg[ZhxemW|c3nu[{BDNVKjZjDWOlAxTSCvdYThcpQh[W6mIIfpcIQhfHmyZTDSZZMtKEmFNUC9NE42KM7:TR?= NHTRbJUzOjhyOEmxNS=>
human A375 cells NV7jSFJKTnWwY4Tpc44h[XO|YYm= M3XhTmlvcGmkaYTpc44hd2ZiYj3SZYYhcW5iaIXtZY4hSTN5NTDj[YxteyCjc4Pld5Nm\CCyaH;zdIhwenmuYYTpc44hd2ZiRWLLMEBKSzVyPUGg{txO MYmyNlgxQDlzMR?=

多くの細胞株試験データを見る場合、クリックしてください

体内試験 In GDC-0879 treated mice, both cell line- and patient-derived BRAFV600E tumors exhibit stronger and more sustained pharmacodynamic inhibition (>90% for 8 hours) and improved survival compared to mutant KRAS-expressing tumors. Although there is involvement of activated RAF signaling in RAS-induced tumorigenesis, decreased time to progression is observed for some KRAS-mutant tumors following GDC-0879 administration. Whereas GDC-0879-mediated efficacy is associated strictly with B-RafV600E status, MEK inhibition also attenuates proliferation and tumor growth of cell lines expressing wild-type BRAF (81% KRAS mutant, 38% KRAS wild type). The responsiveness of B-RafV600E melanoma cells to GDC-0879 could be dramatically altered by pharmacologic and genetic modulation of PI3K pathway activity. [2]

お薦めの試験操作(参考用のみ)

動物試験:[2]
+ 展開
  • 動物モデル: Female nu/nu mice
  • 製剤: 0.5% methylcellulose/0.2% Tween 80
  • 投薬量: 100 mg/kg
  • 投与方法: Oral gavage
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 66 mg/mL (197.38 mM) warming
Ethanol 5 mg/mL (14.95 mM)
Water Insoluble
体内 順序で溶剤を入れること:
0.5% methylcellulose+0.2% Tween 80
30 mg/mL

* 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 334.37
化学式

C19H18N4O2

CAS No. 905281-76-7
保管
in solvent
別名 AR-00341677

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

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

Raf信号経路図

Raf Inhibitors with Unique Features

相関Raf製品

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID