Quizartinib (AC220)

製品コードS1526

Quizartinib (AC220)化学構造

分子量(MW):560.67

Quizartinib (AC220)は一種の第二代FLT3阻害剤で、MV4-11と RS411細胞にFlt3(ITD/WT)に作用する時のIC50値が1.1 nM/4.2 nMです。Quizartinib (AC220)は、Flt3に作用する選択性はKIT、PDGFRA、PDGFRB、RETとCSF-1Rに作用する選択性より10倍が高くなります。臨床3期。

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カスタマーフィードバック(4)

  • Cotreatment with JQ1 and AC220 synergistically induces apoptosis of FLT3-ITD–expressing AML cells. MV4-11 cells were treated with the indicated concentrations of AC220 and/or JQ1 for 24 hours. At the end of treatment, immunoblot analyses were conducted as indicated. The numbers beneath the blots represent densitometry analysis conducted on representative blots.

    Mol Cancer Ther 2014 13(10), 2315-27. Quizartinib (AC220) purchased from Selleck.

    Crude membranes from High-Five insect cells expressing ABCB1 and MCF-7 FLV1000 cells expressing ABCG2 were incubated with 0–30 uM quizartinib for 5 minutes at 21–23°C in 50 mM Tris-HCl, pH 7.5 and 3–6 nM [125I]-IAAP (2200 Ci/mmole) was added. Representative autoradiograms from one experiment are shown in the upper panels; similar results were obtained in two additional experiments. In the lower panels, incorporation of [125I]-IAAP (from autoradiogram, Y-axis) into the ABCB1 and ABCG2 bands was plotted as a function of quizartinib concentration (X-axis). Quizartinib inhibited [125I]-IAAP binding to ABCB1 and ABCG2 with IC50’s of 3.3 uM and 0.07 uM, respectively, and the latter correspond to a therapeutically relevant plasma concentration. Values are from a representative experiment among three independent experiments.

    PLoS One 2013 8(8), e71266. Quizartinib (AC220) purchased from Selleck.

  • The effect of the FLT3 inhibitor AC220 (2nM) on the expression of MYC and E2F1 in MOLM-13 and MV4;11 cells. Cells were treated with vehicle and the FLT3 specific inhibitor AC220 for 24 hM, and then the mRNA and protein levels of MYC and E2F1 were tested.

    Leuk Lymphoma, 2017. Quizartinib (AC220) purchased from Selleck.

    Effect of AC220 on the sensitivity of KB-C2 cells to paclitaxel. The figure showes the survival curves of cells at different concentrations of paclitaxel with or without AC220.  Cell viability was determined by MTT Assay.  KB-3-1 is epidermoid carcinoma cell line while KB-C2 is ABCB1 (P-gp) overexpressing drug (cholchicine) selected cell line. VERA (Verapamil) was used as a positive control of ABCB1 inhibitor.

    Quizartinib (AC220) purchased from Selleck.

製品安全説明書

FLT3阻害剤の選択性比較

生物活性

製品説明 Quizartinib (AC220)は一種の第二代FLT3阻害剤で、MV4-11と RS411細胞にFlt3(ITD/WT)に作用する時のIC50値が1.1 nM/4.2 nMです。Quizartinib (AC220)は、Flt3に作用する選択性はKIT、PDGFRA、PDGFRB、RETとCSF-1Rに作用する選択性より10倍が高くなります。臨床3期。
特性 The most potent cellular FLT3-ITD inhibitor.
靶点
FLT3 (ITD) [1]
(MV4-11 cells)
FLT3 (WT) [1]
(RS4;11 cells)
1.1 nM 4.2 nM
In vitro試験

AC220, a unique, potent and selective inhibitor of FLT3, has high affinity for FLT3 with a Kd value of 1.6 nM. AC220 inhibits the autophosphorylation of FLT3 in the human leukemia cell lines MV4-11 which harbor a homozygous FLT3-ITD mutation and is FLT3 dependent, and RS4;11 which expresses wild-type FLT3 with IC50 values of 1.1 nM and 4.2 nM, respectively. AC220 is the most potent cellular FLT3-ITD inhibitor, leading to the most significant inhibition of MV4-11 cell proliferation with IC50 of 0.56 nM compared to all other FLT3 inhibitors whose IC50 values range from 0.87 nM to 64 nM. AC220 has no inhibitory activity against the proliferation of A375 cells which harbor an activating mutation in BRAF and are not FLT3 dependent, indicating a large window between FLT3 inhibition and general cytotoxic effects. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HL60/VCR MYrGeY5kfGmxbjDBd5NigQ>? M2DvSlAvOS1zMDFOwG0> M3;rfFMxKG2rbh?= M{TCeoVvcGGwY3XzJJVxfGGtZTDv[kB{fWK|dILheIV{KG:oIFHCR2czKGGwZDDBRmNDOSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? MYeyN|k3PzF5Nx?=
K562/ABCB1 NF\MbGhHfW6ldHnvckBCe3OjeR?= M2fLcVAvOS1zMDFOwG0> M{LoVFMxKG2rbh?= MU\lcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MmG4NlM6PjdzN{e=
8226/MR20  M33pSGZ2dmO2aX;uJGF{e2G7 MmXiNE4yNTFyIN88US=> MkPPN|AhdWmw M1zuNIVvcGGwY3XzJJVxfGGtZTDv[kB{fWK|dILheIV{KG:oIFHCR2czKGGwZDDBRmNDOSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? M2n2ZVI{QTZ5MUe3
K562/ABCG2 NIjyU5hHfW6ldHnvckBCe3OjeR?= MlfZNE4yNTFyIN88US=> MWWzNEBucW5? MVrlcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> MWSyN|k3PzF5Nx?=
MCF-7 FLV1000 MUXLbY5ie2ViQYPzZZk> MoLQNQKBmzNyINM1US=> MVG1JI1qdg>? NGX6Nnhl\WO{ZXHz[ZMhYzF{NVndMWlCSVBicHjveI9t[WKnbHnu[{Bw\iCDQlPCNUBifCCLQ{WwJI9nKDNwMzFOwG0> NX32fY9XOjN7NkexO|c>
MCF-7 FLV1000 NUS0VINXU2mwYYPlJGF{e2G7 NGjxSHEx6oDVM{CgxtVO M1fZNlUhdWmw Ml\G[IVkemWjc3XzJHsyOjWLXT3JRWFRKHCqb4TvcIFj\Wyrbnegc4YhSUKFQkKgZZQhUUN3MDDv[kAxNjB5IN88US=> M{i1cVI{QTZ5MUe3
K562/ABCG2 M4PGNmNmdGxiVnnhZoltcXS7IFHzd4F6ew>? NXG2XWV6OC5zL{CuOU8yKML3TR?= NHXyXpY6PiCq Mn20d4Vve2m2aYrld{BMPTZ{L1HCR2czKGOnbHzzJJRwKG2rdH;4ZY51em:wZTD0c5BwfGWlYX9CpC=> MlSwNlM6PjdzN{e=
8226/MR20 M2jYO2NmdGxiVnnhZoltcXS7IFHzd4F6ew>? NX7yRmZFOC5zINM1US=> NHfVfHA6PiCq NFPzfXJ{\W6|aYTpfoV{KEt3NkKvRWJETzJiY3XscJMhfG9ibXn0c5hidnS{b37lJJRweG:2ZXPhcuKh NXPt[ldLOjN7NkexO|c>
HMC1.1 NIrreGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTu[GhVUUN3ME2xOEBvVQ>? NWr1dpJPOjN2OUezNVc>
HMC1.2 M{fESGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXjJR|UxRTF5Mkegcm0> NXuyRYJUOjN2OUezNVc>
p815 M1PCVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVS4dXpwUUN3ME20OFUhdk1? MViyN|Q6PzNzNx?=
Kasumi-1 NYTNNpBuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkTVTWM2OD1|NjDuUS=> MoLVNlM1QTd|MUe=
M-07e + SCF NYjOe2hRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWjmV5JRUUN3ME23O{BvVQ>? NYHF[Is2OjN2OUezNVc>
EOL-1 M{XaUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2excmlEPTB;MTDuUS=> MojqNlM1QTd|MUe=
MV4;11 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3nsOmlEPTB:IEGgcm0> M2rOSlI{PDl5M{G3
MOLM14 NHTUfm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlfJTWM2ODxiMTDuUS=> Mn;yNlM1QTd|MUe=
Pat.221 NVznU416T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrSXlZKSzVyPU[3OUBvVQ>? M4rFN|I{PDl5M{G3
Pat.279 NWHBW5ZJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYD3doFuUUN3ME2zOFM1KG6P NF3hUIEzOzR7N{OxOy=>
Pat.299 NYm0RYR1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYrJR|UxRTd{NEigcm0> MXSyN|Q6PzNzNx?=
Pat.305 NEHSV5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVrjbpJrUUN3ME23NFc6KG6P MYmyN|Q6PzNzNx?=
Pat.375 Ml:zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXzJR|UxRTVyMzDuUS=> MWqyN|Q6PzNzNx?=
Pat.379 MomzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfMTWM2OD16ME[gcm0> NYSwb5VwOjN2OUezNVc>
Pat.368 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHWw[IxKSzVyPUK3NFAhdk1? M4DVTVI{PDl5M{G3
Pat.601 Mnq1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUOwVGxSUUN3ME2xNVU{KG6P MoDpNlM1QTd|MUe=
HMC1.1 MknqRZBweHSxc3nzJGF{e2G7 MmP2TWM2OD1|MTDuUS=> MXWyN|Q6PzNzNx?=
p815 M{DQb2Fxd3C2b4Ppd{BCe3OjeR?= M3K5fGlEPTB;M{SxJI5O M4jCc|I{PDl5M{G3
Kasumi-1 MW\BdI9xfG:|aYOgRZN{[Xl? NWDDOGk3UUN3ME22O{BvVQ>? NEHidXQzOzR7N{OxOy=>
M-07e + SCF M3TaUGFxd3C2b4Ppd{BCe3OjeR?= NX\qXWozUUN3ME23PEBvVQ>? Mn3lNlM1QTd|MUe=
EOL-1 NU\oVIF1SXCxcITvd4l{KEG|c3H5 NEG1V4RKSzVyPDCxJI5O M{DEXFI{PDl5M{G3
MV4;11 M1\udWFxd3C2b4Ppd{BCe3OjeR?= M2\iXWlEPTB;MjDuUS=> NWLqTXFsOjN2OUezNVc>
MOLM14 MkjqRZBweHSxc3nzJGF{e2G7 MoXETWM2OD1|IH7N M3L0PVI{PDl5M{G3
GIST822 NGHKeXpCeG:ydH;zbZMhSXO|YYm= Mo\wTWM2OD1zMEmgcm0> MnLrNlM1QTd|MUe=
Pat.368 MULBdI9xfG:|aYOgRZN{[Xl? NGDuUlRKSzVyPUK5PVghdk1? NGrF[2IzOzR7N{OxOy=>
Pat.601 NGnQcmZCeG:ydH;zbZMhSXO|YYm= M2\4NGlEPTB;OEe2JI5O Ml3ZNlM1QTd|MUe=
MV4-11 NV31T4NRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfTO|IhcA>? M3vJXWlEPTB;MD6zJI5O MmP1NlM1OTJ7M{G=
MOLM-14 NXXrNYtET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3:2PVczKGh? MXXJR|UxRTBwMTDuUS=> MojqNlM1OTJ7M{G=
SEM-K2 NWLZR|hjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIricno4OiCq MXjJR|UxRTBwNDDuUS=> Ml3vNlM1OTJ7M{G=
RS4;11 M4XpNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUS3NkBp MlTrTWM2OD5zMDywNFAhdk1? M1PMR|I{PDF{OUOx
THP-1 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{DkWVczKGh? M3L4WmlEPTB-MUCsNFAxKG6P M{TJbVI{PDF{OUOx
MV4-11 MmP0RZBweHSxc3nzJGF{e2G7 NHzvWo05NzJ2IHi= NVPBTotEcW6mdXPld{B{cWewaX\pZ4FvfCCjbnSg[I9{\S2mZYDlcoRmdnRiUFHSVEBkdGWjdnHn[UBidmRiYXPjeY12dGG2aX;uJI9nKHO3Yj2yUkBFVkF? MoOyNlM1OTJ7M{G=
MOLM-14 MljpRZBweHSxc3nzJGF{e2G7 Ml3rPE8zPCCq NWfHTXlWcW6mdXPld{B{cWewaX\pZ4FvfCCjbnSg[I9{\S2mZYDlcoRmdnRiUFHSVEBkdGWjdnHn[UBidmRiYXPjeY12dGG2aX;uJI9nKHO3Yj2yUkBFVkF? NHLNT4czOzRzMkmzNS=>
SEM-K2 Mn3nRZBweHSxc3nzJGF{e2G7 MXu4M|I1KGh? NUnwU2VbcW6mdXPld{B{cWewaX\pZ4FvfCCjbnSg[I9{\S2mZYDlcoRmdnRiUFHSVEBkdGWjdnHn[UBidmRiYXPjeY12dGG2aX;uJI9nKHO3Yj2yUkBFVkF? NVrRZZRqOjN2MUK5N|E>
MV4-11 MoezS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY[3NkBp M{\xdmlEPTB;MD61OkDDuSByLkOgcm0> M{HJblE6PjV2NEC4
A375 M3jGcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGe3dGQ4OiCq MnzOTWM2OD5iMUCgNFAxKG6P NEjSNJIyQTZ3NESwPC=>

... Click to View More Cell Line Experimental Data

In vivo試験 Oral administration of AC220 (10 mg/kg) induces time-dependent inhibition of FLT3 autophosphorylation in the FLT3-ITD–dependent MV4-11 tumor xenograft mouse model; the inhibition being 90% at 2 hours and 40% at 24 hours. AC220 significantly extends survival in a mouse model of FLT3-ITD AML with doses as low as 1 mg/kg given orally once a day. Treatment with AC220 at 10 mg/kg for 28 days results in rapid and complete regression of tumors in all mice with no tumor regrowth during the 60-day posttreatment period. AC220 displays more significant efficacy compared to sunitinib treatment which causes tumors to shrink slowly and resume growth immediately upon discontinuation of treatment in all but one of the mice. [1]

プロトコル(参考用のみ)

キナーゼアッセイ:[1]
+ 展開

Inhibition of FLT3 autophosphorylation:

To measure inhibition of FLT3 autophosphorylation, MV4-11 or RS4;11 cells are cultured in low serum media (0.5% FBS) overnight and seeded at a density of 400 000 cells per well in a 96-well plate the following day. The cells are incubated with different concentrations of AC220 for 2 hours at 37 °C. To induce FLT3 autophosphorylation in RS4;11 cells, 100 ng/mL FLT3 ligand is added for 15 minutes after the 2-hour AC220 incubation. Cell lysates are prepared and incubated in 96-well plates precoated with a total FLT3 capture antibody. The coated plates are incubated with either a biotinylated antibody against FLT3 to detect total FLT3 or an antibody against phosphotyrosines to detect FLT3 autophosphorylation. In both cases, a SULFO-tagged streptavidin secondary antibody is used for electrochemiluminescence detection on the Meso Scale Discovery platform. The concentration of AC220 that inhibits FLT3-ITD or TLT3-WT autophosphorylation by 50% represents IC50 value
細胞アッセイ: [1]
+ 展開
  • 細胞株: MV4-11 and RS4;11 cells
  • 濃度: Dissolved in DMSO, final concentration ~20 μM
  • 反応時間: 72 hours
  • 実験の流れ: Cells are cultured overnight in low serum media (0.5% FBS), seeded in a 96-well plate at 40 000 cells per well and exposed to AC220 for 72 hours at 37 °C. Cell viability is measured using the Cell Titer-Blue Cell Viability Assa
    (参考用のみ)
動物実験:[1]
+ 展開
  • 動物モデル: Female NU/NU or severe combined immunodeficient mice implanted with MV4-11 cells
  • 製剤: Formulated in 22% hydroxypropyl-β-cyclodextrin
  • 投薬量: ~10 mg/kg
  • 投与方法: Oral gavage
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 33.2 mg/mL (59.21 mM)
Water <0.3 mg/mL <0.3
Ethanol <0.5 mg/mL <0.5
体内 15% Captisol 30 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 560.67
化学式

C29H32N6O4S

CAS No. 950769-58-1
保管
in solvent
別名 N/A

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
NCT02984995 Recruiting Leukemia, Myeloid, Acute Daiichi Sankyo Co., Ltd.|Daiichi Sankyo Inc. December 2016 --
NCT02668653 Recruiting Acute Myeloid Leukemia|Leukemia Daiichi Sankyo Inc. September 2016 Phase 3
NCT02834390 Recruiting Acute Myeloid Leukemia Daiichi Sankyo Co., Ltd.|Daiichi Sankyo Inc. July 2016 Phase 1
NCT02675478 Recruiting Relapsed AML|Refractory AML Daiichi Sankyo Co., Ltd.|Daiichi Sankyo Inc. February 2016 Phase 1
NCT02272478 Recruiting Acute Myeloid Leukaemia|Myelodysplastic Syndrome Cardiff University|Cancer Research UK October 2014 Phase 3
NCT02039726 Recruiting AML Daiichi Sankyo Inc. April 2014 Phase 3

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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID