Quizartinib (AC220)

For research use only.

Catalog No.S1526

94 publications

Quizartinib (AC220) Chemical Structure

CAS No. 950769-58-1

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. Quizartinib (AC220) induces apoptosis of tumor cells. Phase 3.

Selleck's Quizartinib (AC220) has been cited by 94 publications

Purity & Quality Control

Choose Selective Target Protein Ligand Inhibitors

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. Quizartinib (AC220) induces apoptosis of tumor cells. 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
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8226/MR20  NH3pZVJHfW6ldHnvckBCe3OjeR?= MoSxNE4yNTFyIN88US=> NGT6O3o{OCCvaX6= MUDlcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI> NE\MNVI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2O|E4Pyd-MkO5OlcyPzd:L3G+
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MCF-7 FLV1000 MlPPT4lv[XOnIFHzd4F6 MVqw5qCUOzBiwsXN NXjnZ3JQPSCvaX6= MoTF[IVkemWjc3XzJHsyOjWLXT3JRWFRKHCqb4TvcIFj\Wyrbnegc4YhSUKFQkGgZZQhUUN3MDDv[kA{NjNizszN MkHwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NkexO|coRjJ|OU[3NVc4RC:jPh?=
MCF-7 FLV1000 NFPOTJNMcW6jc3WgRZN{[Xl? Mli1NQKBmzNyINM1US=> Mn;kOUBucW5? M13zNoRm[3KnYYPld{BcOTJ3SW2tTWFCWCCyaH;0c4xi[mWuaX7nJI9nKEGEQ1KyJIF1KEmFNUCgc4YhOC5yNzFOwG0> NIXVU4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2O|E4Pyd-MkO5OlcyPzd:L3G+
K562/ABCG2 Mn7SR4VtdCCYaXHibYxqfHliQYPzZZl{ MlH6NE4yNzBwNT:xJOK2VQ>? NI\CV|c6PiCq Ml7ad4Vve2m2aYrld{BMPTZ{L1HCR2czKGOnbHzzJJRwKG2rdH;4ZY51em:wZTD0c5BwfGWlYX9CpC=> NXT1T|k6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OlcyPzdpPkKzPVY4OTd5PD;hQi=>
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MV4;11 M4\2XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoTGTWM2ODxiMTDuUS=> NEPSWGk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O|MyPyd-MkO0PVc{OTd:L3G+
MOLM14 MnK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPGcGZjUUN3MEygNUBvVQ>? Ml7XQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ|NEm3N|E4RC:jPh?=
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Pat.368 NFLKdW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWCxPW86UUN3ME2yO|AxKG6P NFy0TVA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O|MyPyd-MkO0PVc{OTd:L3G+
Pat.601 NYHQVIpMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFm5UlZKSzVyPUGxOVMhdk1? MmHNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ|NEm3N|E4RC:jPh?=
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M-07e + SCF M3zU[mFxd3C2b4Ppd{BCe3OjeR?= MXTJR|UxRTd6IH7N NV3ie4pkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
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MV4-11 NFTIOW1HfW6ldHnvckBie3OjeR?= NXv4d3dMOC5yMTD0c{AyODBibl2= M3yxRlEhcHJ? MUDJcohq[mm2aX;uJI9nKE[OVEOgTXRFKG23dHHueEBqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4hTVKNMT:yJJBpd3OyaH;yfYxifGmxbjDheEBVOjB{L2myNFQh[XRiMD6wNUB1dyBzMECgcm0h[W[2ZYKgNUBpeiCkeTDpcY12dm:kbH;0JIFv[Wy7c3nz NXTse2J2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2O|IxPDlpPkK5OlczODR7PD;hQi=>
MV4-11 NGC4R|lHfW6ldHnvckBie3OjeR?= NEnhNoIyOCCvZz;r[y=> Mk\RNlQhcHK| MVHJckB3cX[xIHnubIljcXSrb36gc4YhTkyWMzDJWGQhdXW2YX70JIlvKGi3bXHuJG1XPC1zMTDj[YxteyC6ZX7v[5Ji\nSnZDDpckBifGi7bXnjJI52N263IH3veZNmKGG|c3Xzd4VlKGG|IHTlZ5Jm[XOnIHnuJHNVSVR3IIDoc5NxcG:{eXzheIlwdiCjdDDZOlk1KGG2IEGwJI1oN2upLDDpdEBi\nSncjCyOEBpenNiYomgbY1ufW6xYnzveEBu\XSqb3SgdoVt[XSrdnWgeI8h[2:wdILvcC=> MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ5MkC0PUc,Ojl4N{KwOFk9N2F-
MV4-11 M2LGO2Z2dmO2aX;uJIF{e2G7 Mn7NNE4yKHWP NW\iXZRSPCCqcoO= MYXJcohq[mm2aX;uJI9nKE[OVEOgbY4hcHWvYX6gUXY1NTFzIHPlcIx{KGG|c3Xzd4VlKGG|IILl[JVkfGmxbjDpckBCU1RicHjvd5Bpd3K7bHH0bY9vKGG2IGPldlQ4OyC{ZYPp[JVmKGG2IECuNUB2VSCjZoTldkA1KGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN? MlvFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl6OUS5OFQoRjJ7OEm0PVQ1RC:jPh?=
MV4-11 MXzGeY5kfGmxbjDhd5NigQ>? NGDjWZQxNjFidV2= MknUOEBpenN? NYnzZ4c2UW6qaXLpeIlwdiCxZjDGUHQ{KGmwIHj1cYFvKE2YND2xNUBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iU2TBWFUheGixc4Doc5J6dGG2aX;uJIF1KFS7ck[5OEBz\XOrZIXlJIF1KDBwMTD1UUBi\nSncjC0JIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM> NETtS2s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUi5OFk1PCd-Mkm4PVQ6PDR:L3G+
MV4-11 MVTGeY5kfGmxbjDhd5NigQ>? MUmwMlEhfU1? MkPaOEBpenN? M4PPWmlvcGmkaYTpc44hd2ZiRlzUN{BqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKEWUS{GvNkBxcG:|cHjvdplt[XSrb36gZZQhXGi{MkCyM3R6ejJyNDDy[ZNq\HWnczDheEAxNjFidV2gZYZ1\XJiNDDodpMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz NFTHXYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUi5OFk1PCd-Mkm4PVQ6PDR:L3G+
MV4-11 MoLQSpVv[3Srb36gZZN{[Xl? NWXKd2tpOC5zIIXN MW[0JIhzew>? NETCZppKdmirYnn0bY9vKG:oIF\MWFMheGixc4Doc5J6dGG2aX;uJIF1KFS7ckW4PU82QTFicnXzbYR2\XNiaX6gbJVu[W5iTW[0MVEyKGOnbHzzJIF1KDBwMTD1UUBi\nSncjC0JIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM> M1rD[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OEm0PVQ1Lz5{OUi5OFk1PDxxYU6=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
phospho-FLT3 / FLT3; 

PubMed: 22875611     


(B) The same cells were also harvested for Western blot analysis after treatment for 90 min with different concentrations of AC220. The phosphorylation of the different FLT3 proteins was determined using a phospho-FLT3 antibody.

p-STAT5 / STAT5 / β-catenin / p-AKT / AKT / p-ERK / ERK / p-S6 / S6; 

PubMed: 28625976     


Western blot analysis of AC220 treated MV4-11 cells. Cells were starved for overnight and treated with AC220 at indicated concentrations. Cells were harvested after 2 hours treatment and lysed. Then western blots analysis was performed. The quantification of bands are shown below the gel.

22875611 28625976
Immunofluorescence
WGA / FLT3 ; 

PubMed: 28895560     


Immunofluorescence staining of FLT3-WT, FLT3 mutants or empty vector with or without AC220 treatment in transiently transfected U2OS cells. WGA (wheat germ agglutinin). Scale bar: 25 μm.

28895560
Growth inhibition assay
Cell viability; 

PubMed: 23967177     


K562/ABCB1 and K562/ABCG2 cells exhibit collateral sensitivity toquizartinib. K562, K562/ABCB1 and K562/ABCG2 cells were plated in the presence of quizartinib in increasing concentrations for 96 hours and viable cells were measured using the WST-1 assay.

23967177
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:[1]
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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:[1]
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  • 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:[1]
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  • Animal Models: Female NU/NU or severe combined immunodeficient mice implanted with MV4-11 cells
  • Dosages: ~10 mg/kg
  • Administration: Oral gavage
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 33 mg/mL (58.85 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
15% Captisol
For best results, use promptly after mixing.
30 mg/mL

* 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
Smiles CC(C)(C)C1=CC(=NO1)NC(=O)NC2=CC=C(C=C2)C3=CN4C5=C(C=C(C=C5)OCCN6CCOCC6)SC4=N3

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Step 2: Enter the in vivo formulation ()
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04459598 Completed Drug: Efavirenz|Drug: Quizartinib Healthy Subjects|Drug-drug Interaction|Pharmacokinetics|Quizartinib Daiichi Sankyo Co. Ltd.|Daiichi Sankyo Inc. September 8 2020 Early Phase 1
NCT04473664 Completed Drug: Quizartinib Hepatic Impairment|Moderate Impaired Hepatic Function Daiichi Sankyo Co. Ltd.|Daiichi Sankyo Inc. September 29 2020 Phase 1
NCT04459585 Completed Drug: Dabigatran Etexilate Mesylate|Drug: Quizartinib Healthy Subjects|Drug-drug Interaction|Pharmacokinetics|Quizartinib Daiichi Sankyo Co. Ltd.|Daiichi Sankyo Inc. August 28 2020 Early Phase 1
NCT04209725 Terminated Drug: CPX-351|Drug: Quizartinib Leukemia Myeloid Acute SCRI Development Innovations LLC June 3 2020 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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Frequently Asked Questions

  • Question 1:

    Is it possible to alter the captisol concentration to make it more dissolvable i.e 20% or 25% captisol ?

  • Answer:

    In 15% Captisol, the compound forms s suspension at 30mg/ml. Increasing the percentage of Captisol will not convert the mixture into solution. You can use suspension for oral gavage feeding.

Target Protein Ligand Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID