Quizartinib (AC220)

Catalog No.S1526

Quizartinib (AC220) Chemical Structure

Molecular Weight(MW): 560.67

Quizartinib (AC220) is a second-generation FLT3 inhibitor for Flt3(ITD/WT) with IC50 of 1.1 nM/4.2 nM in MV4-11 and RS4;11 cells, respectively, 10-fold more selective for Flt3 than KIT, PDGFRα, PDGFRβ, RET, and CSF-1R. Phase 3.

Size Price Stock Quantity  
In DMSO USD 353 In stock
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USD 370 In stock
USD 970 In stock

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3 Customer Reviews

  • 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.

  • 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.

Purity & Quality Control

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description Quizartinib (AC220) is a second-generation FLT3 inhibitor for Flt3(ITD/WT) with IC50 of 1.1 nM/4.2 nM in MV4-11 and RS4;11 cells, respectively, 10-fold more selective for Flt3 than KIT, PDGFRα, PDGFRβ, RET, and CSF-1R. Phase 3.
Features The most potent cellular FLT3-ITD inhibitor.
Targets
FLT3 (ITD) [1]
(MV4-11 cells)
FLT3 (WT) [1]
(RS4;11 cells)
1.1 nM 4.2 nM
In vitro

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 NXf6TXZ2TnWwY4Tpc44hSXO|YYm= NXjac3ZHOC5zLUGwJO69VQ>? NXL0dHZVOzBibXnu NXfDV|ZU\W6qYX7j[ZMhfXC2YXvlJI9nKHO3YoP0doF1\XNib3[gRWJETzJiYX7kJGFDS0JzIHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{ M2\HU|I{QTZ5MUe3
K562/ABCB1 MYPGeY5kfGmxbjDBd5NigQ>? NYrP[2RjOC5zLUGwJO69VQ>? NYXacY9nOzBibXnu Mnqy[Y5p[W6lZYOgeZB1[WunIH;mJJN2[nO2cnH0[ZMhd2ZiQVLDS|Ih[W6mIFHCR2IyKGmwIHGgZ49v[2WwdILheIlwdi2mZYDlcoRmdnRibXHucoVz NWHXfI5ROjN7NkexO|c>
8226/MR20  NWTBeJpYTnWwY4Tpc44hSXO|YYm= MU[wMlEuOTBizszN NEmwZXM{OCCvaX6= MWjlcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> M3TITlI{QTZ5MUe3
K562/ABCG2 MlvZSpVv[3Srb36gRZN{[Xl? NHrBOYMxNjFvMUCg{txO MmjyN|AhdWmw MUHlcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NHHS[GwzOzl4N{G3Oy=>
MCF-7 FLV1000 NVzvZ2lYU2mwYYPlJGF{e2G7 NFuz[Hcx6oDVM{CgxtVO NXv1VpA1PSCvaX6= MVfk[YNz\WG|ZYOgX|EzPUmfLVnBRXAheGixdH;sZYJmdGmwZzDv[kBCSkOEMTDheEBKSzVyIH;mJFMvOyEQvF2= Mlm1NlM6PjdzN{e=
MCF-7 FLV1000 Mnj4T4lv[XOnIFHzd4F6 NWHNcVBNOOLCk{OwJOK2VQ>? NHTI[W82KG2rbh?= Mn;t[IVkemWjc3XzJHsyOjWLXT3JRWFRKHCqb4TvcIFj\Wyrbnegc4YhSUKFQkKgZZQhUUN3MDDv[kAxNjB5IN88US=> MViyN|k3PzF5Nx?=
K562/ABCG2 M4\kbGNmdGxiVnnhZoltcXS7IFHzd4F6ew>? M4PXUlAvOS9yLkWvNUDDvU1? MWO5OkBp Ml;vd4Vve2m2aYrld{BMPTZ{L1HCR2czKGOnbHzzJJRwKG2rdH;4ZY51em:wZTD0c5BwfGWlYX9CpC=> MkfkNlM6PjdzN{e=
8226/MR20 MUnD[YxtKF[rYXLpcIl1gSCDc4PhfZM> MWKwMlEhyrWP M3zXZVk3KGh? M3faVpNmdnOrdHn6[ZMhUzV4Mj;BRmNIOiClZXzsd{B1dyCvaYTvfIFvfHKxbnWgeI9xd3SnY3HuxsA> MWqyN|k3PzF5Nx?=
HMC1.1 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFjYfVNKSzVyPUG0JI5O NEf4OW8zOzR7N{OxOy=>
HMC1.2 NXPvVZlXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXnJR|UxRTF5Mkegcm0> MlSyNlM1QTd|MUe=
p815 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NInydlBKSzVyPUS0OUBvVQ>? NWm4TFZROjN2OUezNVc>
Kasumi-1 NUDvephoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHXTWM2OD1|NjDuUS=> NIHzXo0zOzR7N{OxOy=>
M-07e + SCF NUDyWnR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4HyRmlEPTB;N{egcm0> NUHnVJZsOjN2OUezNVc>
EOL-1 MkOyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEGyNHNKSzVyPUGgcm0> NVnnXJlzOjN2OUezNVc>
MV4;11 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVfJR|UxRCBzIH7N NEKycm0zOzR7N{OxOy=>
MOLM14 NYr2U3pZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\4TWM2ODxiMTDuUS=> MXmyN|Q6PzNzNx?=
Pat.221 Mnn5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2n4cmlEPTB;Nke1JI5O MX:yN|Q6PzNzNx?=
Pat.279 NImyXmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPXTWM2OD1|NEO0JI5O MVuyN|Q6PzNzNx?=
Pat.299 M{H5cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUnJR|UxRTd{NEigcm0> M3Hsb|I{PDl5M{G3
Pat.305 NGHzc5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NETIPZdKSzVyPUewO|khdk1? MWiyN|Q6PzNzNx?=
Pat.375 NF3MO4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn\wTWM2OD13MEOgcm0> NWTXVFZMOjN2OUezNVc>
Pat.379 M{PIbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NG\Ie|ZKSzVyPUiwOkBvVQ>? MWGyN|Q6PzNzNx?=
Pat.368 M3L3cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXrOcGozUUN3ME2yO|AxKG6P NXXQNWVIOjN2OUezNVc>
Pat.601 NX;yXXBTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NE\pRWZKSzVyPUGxOVMhdk1? NGXPRW4zOzR7N{OxOy=>
HMC1.1 NYrDRZJ{SXCxcITvd4l{KEG|c3H5 Mke0TWM2OD1|MTDuUS=> MUOyN|Q6PzNzNx?=
p815 NELWOZdCeG:ydH;zbZMhSXO|YYm= MXrJR|UxRTN2MTDuUS=> M3GxblI{PDl5M{G3
Kasumi-1 M3K5OWFxd3C2b4Ppd{BCe3OjeR?= NIXCOXlKSzVyPU[3JI5O MYGyN|Q6PzNzNx?=
M-07e + SCF NUn5UnV3SXCxcITvd4l{KEG|c3H5 NGfkS4hKSzVyPUe4JI5O M3PaT|I{PDl5M{G3
EOL-1 NEfGVnJCeG:ydH;zbZMhSXO|YYm= MkP4TWM2ODxiMTDuUS=> NFXkZ4wzOzR7N{OxOy=>
MV4;11 Ml;3RZBweHSxc3nzJGF{e2G7 MlLGTWM2OD1{IH7N M3TOdFI{PDl5M{G3
MOLM14 M3zST2Fxd3C2b4Ppd{BCe3OjeR?= MnToTWM2OD1|IH7N M37mNVI{PDl5M{G3
GIST822 MWLBdI9xfG:|aYOgRZN{[Xl? NH\RNFBKSzVyPUGwPUBvVQ>? MVWyN|Q6PzNzNx?=
Pat.368 Mnm1RZBweHSxc3nzJGF{e2G7 NYHPRpZwUUN3ME2yPVk5KG6P NEHsSWwzOzR7N{OxOy=>
Pat.601 MVrBdI9xfG:|aYOgRZN{[Xl? NYPTfmsxUUN3ME24O|Yhdk1? NIPRd2QzOzR7N{OxOy=>
MV4-11 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M33EXVczKGh? NH7CN4FKSzVyPUCuN{BvVQ>? NUHKdI1OOjN2MUK5N|E>
MOLM-14 MlT6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnZVGs4OiCq Mle2TWM2OD1yLkGgcm0> NGLpeJMzOzRzMkmzNS=>
SEM-K2 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn;pO|IhcA>? NIe4T5lKSzVyPUCuOEBvVQ>? MWWyN|QyOjl|MR?=
RS4;11 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3O0PVczKGh? NUjkboQyUUN3ME6xNEwxODBibl2= NGPZZ5ozOzRzMkmzNS=>
THP-1 NGSzdFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1rxelczKGh? MUTJR|UxRjFyLECwNEBvVQ>? NWHURWZWOjN2MUK5N|E>
MV4-11 MYLBdI9xfG:|aYOgRZN{[Xl? MmnwPE8zPCCq NYj1OWg{cW6mdXPld{B{cWewaX\pZ4FvfCCjbnSg[I9{\S2mZYDlcoRmdnRiUFHSVEBkdGWjdnHn[UBidmRiYXPjeY12dGG2aX;uJI9nKHO3Yj2yUkBFVkF? MoCxNlM1OTJ7M{G=
MOLM-14 NIH5Z2hCeG:ydH;zbZMhSXO|YYm= MYK4M|I1KGh? MVXpcoR2[2W|IIPp[45q\mmlYX70JIFv\CCmb4PlMYRmeGWwZHXueEBRSVKSIHPs[YF3[WenIHHu[EBi[2O3bYXsZZRqd25ib3[gd5VjNTKQIFTORS=> MlX6NlM1OTJ7M{G=
SEM-K2 NVLjTpVoSXCxcITvd4l{KEG|c3H5 MYq4M|I1KGh? MXPpcoR2[2W|IIPp[45q\mmlYX70JIFv\CCmb4PlMYRmeGWwZHXueEBRSVKSIHPs[YF3[WenIHHu[EBi[2O3bYXsZZRqd25ib3[gd5VjNTKQIFTORS=> MkjoNlM1OTJ7M{G=
MV4-11 NY\YUYd[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4e4dFczKGh? MWLJR|UxRTBwNU[gxtEhOC5|IH7N M3vPR|E6PjV2NEC4
A375 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHzn[FI4OiCq MkD4TWM2OD5iMUCgNFAxKG6P M4XBbFE6PjV2NEC4

... Click to View More Cell Line Experimental Data

In vivo 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]

Protocol

Kinase Assay
+ Expand

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
Cell Research
+ Expand
  • Cell lines: MV4-11 and RS4;11 cells
  • Concentrations: Dissolved in DMSO, final concentration ~20 μM
  • Incubation Time: 72 hours
  • Method: 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
    (Only for Reference)
Animal Research
+ Expand
  • Animal Models: Female NU/NU or severe combined immunodeficient mice implanted with MV4-11 cells
  • Formulation: Formulated in 22% hydroxypropyl-β-cyclodextrin
  • Dosages: ~10 mg/kg
  • Administration: Oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 33.2 mg/mL (59.21 mM)
Water <0.3 mg/mL <0.3
Ethanol <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.

Chemical Information

Molecular Weight 560.67
Formula

C29H32N6O4S

CAS No. 950769-58-1
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02834390 Not yet recruiting Acute Myeloid Leukemia Daiichi Sankyo Co., Ltd.|Daiichi Sankyo Inc. July 2016 Phase 1
NCT02668653 Not yet recruiting Acute Myeloid Leukemia|Leukemia Daiichi Sankyo Inc. March 2016 Phase 3
NCT02675478 Recruiting Relapsed AML|Refractory AML Daiichi Sankyo Co., Ltd.|Daiichi Sankyo Inc. February 2016 Phase 1
NCT02272478 Not yet 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
NCT01892371 Recruiting Leukemia M.D. Anderson Cancer Center|Ambit Biosciences Corporation|Celgene|National Cancer Institute (NCI) November 2013 Phase 1|Phase 2

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID