Quizartinib (AC220) 化学構造
分子量: 560.67

高品質保証

カスタマーフィードバック(3)

Quality Control & MSDS

製品説明

  • Compare FLT3 Inhibitors
    FLT3製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 Quizartinib (AC220)は、FLT3の強力で選択的な阻害剤で、 FLT3-ITDとFLT3-WT自己リン酸化に作用すると、 IC50がそれぞれ 1.1 nM 、4.2 nMになる。
ターゲット Flt3ITD Flt3wt
IC50 1.1 nM [1] 4.2 nM [1]
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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
HL60/VCR NIfkUZdHfW6ldHnvckBCe3OjeR?= MYSwMlEuOTBizszN MUOzNEBucW5? NXPYb4FU\W6qYX7j[ZMhfXC2YXvlJI9nKHO3YoP0doF1\XNib3[gRWJETzJiYX7kJGFDS0JzIHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ NU\OcHpkOjN7NkexO|c>
K562/ABCB1 M3HYXGZ2dmO2aX;uJGF{e2G7 MoLmNE4yNTFyIN88US=> MXKzNEBucW5? MU\lcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NFK0WWUzOzl4N{G3Oy=>
8226/MR20  MWHGeY5kfGmxbjDBd5NigQ>? M37UWFAvOS1zMDFOwG0> NF64eXE{OCCvaX6= M4Dm[oVvcGGwY3XzJJVxfGGtZTDv[kB{fWK|dILheIV{KG:oIFHCR2czKGGwZDDBRmNDOSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>? Mn\vNlM6PjdzN{e=
K562/ABCG2 NYn0SoM1TnWwY4Tpc44hSXO|YYm= MXmwMlEuOTBizszN NWnucIFuOzBibXnu NGjZfFFmdmijbnPld{B2eHSja3Wgc4Yhe3Wkc4TyZZRmeyCxZjDBRmNIOiCjbnSgRWJESjFiaX6gZUBkd26lZX70doF1cW:wLXTldIVv\GWwdDDtZY5v\XJ? M4LxV|I{QTZ5MUe3
MCF-7 FLV1000 M3jjfWtqdmG|ZTDBd5NigQ>? M{DpOVDjiJN|MDFCuW0> M163WFUhdWmw NWL4ZYZ5\GWlcnXhd4V{KFtzMkXJYU1KSUGSIIDoc5RwdGGkZXzpcochd2ZiQVLDRlEh[XRiSVO1NEBw\iB|LkOg{txO MUeyN|k3PzF5Nx?=
MCF-7 FLV1000 NFPHZmJMcW6jc3WgRZN{[Xl? Mlm1NQKBmzNyINM1US=> NFrqT2I2KG2rbh?= MkXs[IVkemWjc3XzJHsyOjWLXT3JRWFRKHCqb4TvcIFj\Wyrbnegc4YhSUKFQkKgZZQhUUN3MDDv[kAxNjB5IN88US=> NUnBcGRmOjN7NkexO|c>
K562/ABCG2 NEXHPHpE\WyuIG\pZYJqdGm2eTDBd5NigXN? M3O0[VAvOS9yLkWvNUDDvU1? M4HlT|k3KGh? MYLz[Y5{cXSrenXzJGs2PjJxQVLDS|Ih[2WubIOgeI8hdWm2b4jhcpRzd26nIITvdI91\WOjbtMg NYDqRo9wOjN7NkexO|c>
8226/MR20 M2XCV2NmdGxiVnnhZoltcXS7IFHzd4F6ew>? NFPyXpExNjFiwsXN MlPYPVYhcA>? M3HITZNmdnOrdHn6[ZMhUzV4Mj;BRmNIOiClZXzsd{B1dyCvaYTvfIFvfHKxbnWgeI9xd3SnY3HuxsA> M4PFZVI{QTZ5MUe3
HMC1.1 M320[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjWTWM2OD1zNDDuUS=> MWKyN|Q6PzNzNx?=
HMC1.2 MlG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXSydlQ5UUN3ME2xO|I4KG6P NYrlWYhNOjN2OUezNVc>
p815 NWewXZhKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3KTWM2OD12NEWgcm0> MWqyN|Q6PzNzNx?=
Kasumi-1 Mlf4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXvJR|UxRTN4IH7N MkTkNlM1QTd|MUe=
M-07e + SCF MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrQTWM2OD15NzDuUS=> NXPOenBKOjN2OUezNVc>
EOL-1 MnvJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3jjfmlEPTB;MTDuUS=> NIf3dpEzOzR7N{OxOy=>
MV4;11 M1HOWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYLJR|UxRCBzIH7N M2SzcFI{PDl5M{G3
MOLM14 MmX5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVvJR|UxRCBzIH7N NYXuVWs5OjN2OUezNVc>
Pat.221 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoS2TWM2OD14N{Wgcm0> MnXZNlM1QTd|MUe=
Pat.279 M1XjTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLwTWM2OD1|NEO0JI5O MnniNlM1QTd|MUe=
Pat.299 NYDsWZU4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEnORVZKSzVyPUeyOFghdk1? NFjKV28zOzR7N{OxOy=>
Pat.305 MkHES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn62TWM2OD15MEe5JI5O M1;FUlI{PDl5M{G3
Pat.375 M1ntOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHzHTIRKSzVyPUWwN{BvVQ>? MWGyN|Q6PzNzNx?=
Pat.379 MoOxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHWTWM2OD16ME[gcm0> NXnr[lE6OjN2OUezNVc>
Pat.368 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnHYTWM2OD1{N{CwJI5O MmS0NlM1QTd|MUe=
Pat.601 M2HJbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjtTWM2OD1zMUWzJI5O MkPBNlM1QTd|MUe=
HMC1.1 MmXmRZBweHSxc3nzJGF{e2G7 MkjLTWM2OD1|MTDuUS=> MUmyN|Q6PzNzNx?=
p815 M3TZdWFxd3C2b4Ppd{BCe3OjeR?= NVHrWGI1UUN3ME2zOFEhdk1? MUWyN|Q6PzNzNx?=
Kasumi-1 MVfBdI9xfG:|aYOgRZN{[Xl? MmTOTWM2OD14NzDuUS=> M1jYNlI{PDl5M{G3
M-07e + SCF NGS5NlBCeG:ydH;zbZMhSXO|YYm= MWXJR|UxRTd6IH7N NYjaN20{OjN2OUezNVc>
EOL-1 M{fJZmFxd3C2b4Ppd{BCe3OjeR?= M3jRc2lEPTB:IEGgcm0> MlrqNlM1QTd|MUe=
MV4;11 MlyyRZBweHSxc3nzJGF{e2G7 M{P1dmlEPTB;MjDuUS=> M2faWlI{PDl5M{G3
MOLM14 NWr4R25XSXCxcITvd4l{KEG|c3H5 NED6Z3NKSzVyPUOgcm0> M4nNPVI{PDl5M{G3
GIST822 M174fGFxd3C2b4Ppd{BCe3OjeR?= MX;JR|UxRTFyOTDuUS=> NHHrOmkzOzR7N{OxOy=>
Pat.368 NIjTVFhCeG:ydH;zbZMhSXO|YYm= M4G3emlEPTB;Mkm5PEBvVQ>? M{j3XVI{PDl5M{G3
Pat.601 NVzuS4oxSXCxcITvd4l{KEG|c3H5 MWTJR|UxRTh5NjDuUS=> NEH3[nEzOzR7N{OxOy=>
MV4-11 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWG3NkBp NIe1PIpKSzVyPUCuN{BvVQ>? M3TOcVI{PDF{OUOx
MOLM-14 MkDpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1fOPFczKGh? NF7GTpVKSzVyPUCuNUBvVQ>? MVGyN|QyOjl|MR?=
SEM-K2 NVTVN3NUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWDPXHNpPzJiaB?= MU\JR|UxRTBwNDDuUS=> MWSyN|QyOjl|MR?=
RS4;11 NWDGO|c5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NU\xbZlYPzJiaB?= NIfWNZpKSzVyPkGwMFAxOCCwTR?= MUKyN|QyOjl|MR?=
THP-1 NYHvWWIyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;CdG53PzJiaB?= MU\JR|UxRjFyLECwNEBvVQ>? MkLpNlM1OTJ7M{G=
MV4-11 MYHBdI9xfG:|aYOgRZN{[Xl? NHK5cnk5NzJ2IHi= MljVbY5lfWOnczDzbYdvcW[rY3HueEBidmRiZH;z[U1l\XCnbnTlcpQhWEGUUDDjcIVifmGpZTDhcoQh[WOldX31cIF1cW:wIH;mJJN2[i1{TjDEUmE> Mn7TNlM1OTJ7M{G=
MOLM-14 NUHrbGRjSXCxcITvd4l{KEG|c3H5 MUi4M|I1KGh? NYDaem1qcW6mdXPld{B{cWewaX\pZ4FvfCCjbnSg[I9{\S2mZYDlcoRmdnRiUFHSVEBkdGWjdnHn[UBidmRiYXPjeY12dGG2aX;uJI9nKHO3Yj2yUkBFVkF? NWfDNFdGOjN2MUK5N|E>
SEM-K2 M2f5dWFxd3C2b4Ppd{BCe3OjeR?= NHnSXWw5NzJ2IHi= M{HE[4lv\HWlZYOgd4lodmmoaXPhcpQh[W6mIHTvd4Uu\GWyZX7k[Y51KFCDUmCgZ4xm[X[jZ3WgZY5lKGGlY4XteYxifGmxbjDv[kB{fWJvMl6gSG5C MXeyN|QyOjl|MR?=
MV4-11 M1LDVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUS3NkBp Ml7hTWM2OD1yLkW2JOKyKDBwMzDuUS=> M3y5T|E6PjV2NEC4
A375 NEewfoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3TObVczKGh? NY\LepozUUN3ME6gNVAhODByIH7N M2XSZVE6PjV2NEC4

... 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]
臨床試験 A Phase I study of AC220 in patients with relapsed/refractory acute myeloid leukemia, regardless of FLT3 status, has been completed.
特集 The most potent cellular FLT3-ITD inhibitor.

プロトコル (参考用のみ)

キナーゼアッセイ: [1]

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]

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

動物実験: [1]

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

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Quizartinib (AC220) SDF
分子量 560.67
化学式

C29H32N6O4S

CAS No. 950769-58-1
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 33.2 mg/mL (59.21 mM)
<0.3 mg/mL <0.3
エタノール <0.5 mg/mL <0.5
In vivo 15% Captisol 30 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 Urea, N-[5-(1,1-dimethylethyl)-3-isoxazolyl]-N'-[4-[7-[2-(4-morpholinyl)ethoxy]imidazo[2,1-b]benzothiazol-2-yl]phenyl]-

カスタマーフィードバック (3)


Click to enlarge
Rating
Source Mol Cancer Ther, 2014, 13(10), 2315-27. Quizartinib (AC220) purchased from Selleck
Method Western blot
Cell Lines MV4-11 cells
Concentrations 20 uM
Incubation Time 24 h
Results Cotreatment with JQ1 and quizartinib resulted in greater inhibition of the levels of p-STAT5, p-AKT, and p-ERK1/2 without significant alterations in the unphosphorylated versions of these proteins.

Click to enlarge
Rating
Source PLoS One, 2013, 8(8), e71266. Quizartinib (AC220) purchased from Selleck
Method Western blot
Cell Lines High-Five insect, MCF-7 FLV1000 cells
Concentrations 0-30 uM
Incubation Time 5 min
Results Since quizartinib inhibited substrate transport by ABCG2 and ABCB1 in a concentration-dependent manner, it sought to confirm that it interacted with established drug-binding sites of these transport proteins. It measured effects of quizartinib on photolabeling of ABCG2 and ABCB1 with [125I]-IAAP. Quizartinib was found to inhibit [125I]-IAAP photolabeling of ABCG2 and ABCB1 with IC50 values of 0.07 礛 and 3.3 礛, respectively.

Click to enlarge
Rating
Source Quizartinib (AC220) purchased from Selleck
Method MTT Assay
Cell Lines epidermoid carcinoma cell line
Concentrations 0.75-3 μM
Incubation Time
Results Effect of AC220 on the sensitivity of KB-C2 cells to paclitaxel.

文献中の引用 (12)

技術サポート&よくある質問(FAQ)

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。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related FLT3 阻害剤

  • Dovitinib (TKI258) Lactate

    Dovitinib (TKI258) Lactate is the Lactate of Dovitinib, which is a multitargeted RTK inhibitor, mostly for class III (FLT3/c-Kit) with IC50 of 1 nM/2 nM, also potent to class IV (FGFR1/3) and class V (VEGFR1-4) RTKs with IC50 of 8-13 nM, less potent to InsR, EGFR, c-Met, EphA2, Tie2, IGFR1 and HER2. Phase 4.

  • AMG 925

    AMG 925 is a potent and orally bioavailable dual FLT3/CDK4 inhibitor with IC50 of 1 nM and 3 nM, respectively.

  • PX-478 2HCl

    PX-478 2HCl is an orally active, and selective hypoxia-inducible factor-1α (HIF-1α) inhibitor. Phase 1.

  • Defactinib (VS-6063, PF-04554878)

    Defactinib (VS-6063, PF-04554878) is a selective, and orally active FAK inhibitor. Phase 2.

  • Dovitinib (TKI-258, CHIR-258)

    Dovitinib (TKI-258, CHIR-258)は非常に強い、新型の多い標的阻害剤、FLT3、c - kit、受容体、マウス/2/3、成長因子受容体と球コロニー刺激因子受容体ßに作用する時、IC50がそれぞれ 1 nM, 2 nM, 5 nM, 10 nM, 8 nM, 27 nM と 36 nMになる。

  • ENMD-2076

    ENMD-2076は、有糸分裂キナーゼ・オーロラAとオーロラBの選択的な阻害剤で、IC50 がそれぞれ 14 nM と 350 nMです。

    Features:Multi-target, anti-proliferative, pro-apoptotic activity, anti-angiogenic.

  • KW-2449

    KW-2449はFLT3とABLキナーゼを抑制、IC50がそれぞれ6.6と14nMになる。

    Features:Investigated as a FLT3 inhibitor in clinical trials, with others in early development.

  • Tandutinib (MLN518)

    Tandutinib (MLN518)は、FLT3、PDGFRとc-キットのATP競争的で非常に選択的な阻害剤で、 IC50がそれぞれ 0.22 μM、0.20 μM 、0.17 μMです。

  • Dovitinib (TKI-258) Dilactic Acid

    Dovitinib (TKI-258) Dilactic Acid is a multitargeted tyrosine kinase inhibitor of FLT3 and c-KIT with IC50 of 1 nM and 2 nM, respectively.

最近チェックしたアイテム

Tags: Quizartinib (AC220)を買う | Quizartinib (AC220)供給者 | Quizartinib (AC220)を購入する | Quizartinib (AC220)費用 | Quizartinib (AC220)生産者 | オーダーQuizartinib (AC220) | Quizartinib (AC220)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ