Quizartinib (AC220)

Name: Quizartinib (AC220)
Brand: Selleck Chemicals
SKU: S1526
Rating: 5 (99 reviews)

For research use only.

Catalog No.S1526

99 publications

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 99 publications

Cancer Cell, 2018, 34(2):315-330

PubMed: 30033091 ( click the link to review the publication )

Nat Med, 2017, 23(1):69-78

PubMed: 27941792 ( click the link to review the publication )

Mol Cell, 2021, S1097-2765(21)00507-4

PubMed: 34289383 ( click the link to review the publication )

Clin Cancer Res, 2021, 10.1158/1078-0432.CCR-20-3458

PubMed: 34103301 ( click the link to review the publication )

Autophagy, 2021, 1-10

PubMed: 33446043 ( click the link to review the publication )

Leukemia, 2021, 10.1038/s41375-021-01308-z

PubMed: 34127794 ( click the link to review the publication )

Cancer Res, 2021, canres.0955.2021

PubMed: 34551960 ( click the link to review the publication )

Cancer Res, 2021, canres.3761.2020

PubMed: 34215619 ( click the link to review the publication )

Blood Cancer J, 2021, 11(3):57

PubMed: 33714981 ( click the link to review the publication )

Protein Cell, 2021, 10.1007/s13238-021-00858-3

PubMed: 34291435 ( click the link to review the publication )

Cancers (Basel), 2021, 13(14)3464

PubMed: 34298678 ( click the link to review the publication )

Cell Death Discov, 2021, 7(1):121

PubMed: 34035227 ( click the link to review the publication )

Cell Chem Biol, 2021, S2451-9456(21)00475-X

PubMed: 34762849 ( click the link to review the publication )

Front Immunol, 2021, 12:699128

PubMed: 34249005 ( click the link to review the publication )

Cancer Discov, 2021, candisc.0738.2020

PubMed: 33436370 ( click the link to review the publication )

Mol Cancer Ther, 2021, 20(4):676-690

PubMed: 33568357 ( click the link to review the publication )

mSphere, 2021, 6(1)e00986-20

PubMed: 33408225 ( click the link to review the publication )

Drug Metab Dispos, 2021, 49(1):53-61

PubMed: 33148688 ( click the link to review the publication )

Cell Signal, 2021, 87:110144

PubMed: 34509612 ( click the link to review the publication )

Oncol Lett, 2021, 21(5):397

PubMed: 33777220 ( click the link to review the publication )

Hum Cell, 2021, 10.1007/s13577-021-00639-4

PubMed: 34731453 ( click the link to review the publication )

Hum Cell, 2021, 10.1007/s13577-021-00579-z

PubMed: 34304386 ( click the link to review the publication )

Thorac Cancer, 2021, 10.1111/1759-7714.13849

PubMed: 33566442 ( click the link to review the publication )

Cell Rep, 2020, 33(1):108221

PubMed: 33027668 ( click the link to review the publication )
Haematologica, 2020, 15 pii: haematol 2019 244020

PubMed: 32414851 ( click the link to review the publication )

Mol Cell Proteomics, 2020, 10.1074/mcp.RA119.001504

PubMed: 32102969 ( click the link to review the publication )

Eur J Med Chem, 2020, 193:112232

PubMed: 32199135 ( click the link to review the publication )

J Cell Mol Med, 2020, 25

PubMed: 32450611 ( click the link to review the publication )

J Cell Mol Med, 2020, 24(3):2308-2318

PubMed: 31881122 ( click the link to review the publication )

Sci Rep, 2020, 10(1):16187

PubMed: 32999332 ( click the link to review the publication )

Sci Rep, 2020, 10(1):1906

PubMed: 32024878 ( click the link to review the publication )

Transl Oncol, 2020, 1;13(4):100766

PubMed: 32247263 ( click the link to review the publication )

Hum Cell, 2020, 10.1007/s13577-020-00420-z

PubMed: 32870449 ( click the link to review the publication )

Cancer Cell, 2020, 38(6):872-890.e6

PubMed: 33217342 ( click the link to review the publication )

Pharmacol Res, 2020, 151:104556

PubMed: 31778791 ( click the link to review the publication )

FEBS Open Bio, 2020, 10.1002/2211-5463.12827

PubMed: 32128992 ( click the link to review the publication )

Sci Transl Med, 2019,

PubMed: 31484791 ( click the link to review the publication )

Autophagy, 2019, 15(9):1558-1571

PubMed: 30821613 ( click the link to review the publication )

Cell Rep, 2019, 28(9):2331-2344

PubMed: 31461650 ( click the link to review the publication )

Cancer Discov, 2019, 9(6):756-777

PubMed: 30862724 ( click the link to review the publication )

Int J Mol Sci, 2019, 20(19)

PubMed: 31554189 ( click the link to review the publication )

Theriogenology, 2019, 126:145-152

PubMed: 30553232 ( click the link to review the publication )

Cell Rep, 2019, 26(11):2916-2928.e13

PubMed: 30865883 ( click the link to review the publication )

Hemasphere, 2019, 3(2):e182

PubMed: 31723821 ( click the link to review the publication )

FEBS Lett, 2019, 593(16):2162-2176

PubMed: 31135968 ( click the link to review the publication )

Oncotarget, 2019, 10(58):6111-6123

PubMed: 31692922 ( click the link to review the publication )

Blood, 2018, 25;131(4):426-438

PubMed: 29187377 ( click the link to review the publication )

Blood, 2018, 132(1):67-77.

PubMed: 29784639 ( click the link to review the publication )
Clin Cancer Res, 2018, 24(7):1716-1726

PubMed: 29330206 ( click the link to review the publication )

Leukemia, 2018, 32(2):313-322

PubMed: 28895560 ( click the link to review the publication )

Haematologica, 2018, haematol.2018.189399

PubMed: 29748445 ( click the link to review the publication )

Clin Cancer Res, 2018, 24(10):2417-2429

PubMed: 29463558 ( click the link to review the publication )

Oncogene, 2018, 37(6):787-797

PubMed: 29059168 ( click the link to review the publication )

mBio, 2018, 9(2)e00682-18

PubMed: 29691342 ( click the link to review the publication )

Cell Death Dis, 2018, 9(2):138

PubMed: 29374185 ( click the link to review the publication )

Neoplasia, 2018, 20(1):1-11

PubMed: 29172076 ( click the link to review the publication )

Nephrol Dial Transplant, 2018, 10.1093/ndt/gfy385

PubMed: 30590794 ( click the link to review the publication )

PLoS One, 2018, 13(1):e0190682

PubMed: 29298347 ( click the link to review the publication )

PLoS One, 2018, 13(5):e0196805

PubMed: 29723246 ( click the link to review the publication )

Exp Hematol, 2018, 58:52-58

PubMed: 28947392 ( click the link to review the publication )

J Ophthalmol, 2018, 2018:2518568

PubMed: 29854425 ( click the link to review the publication )

Oncotarget, 2018, 9(76):34240-34258

PubMed: 30344940 ( click the link to review the publication )

Leukemia, 2018, 32(11):2374-2387

PubMed: 29743719 ( click the link to review the publication )

Oncotarget, 2018, 9(24):16917-16931

PubMed: 29682194 ( click the link to review the publication )

Blood, 2017, 130(1):48-58

PubMed: 28490572 ( click the link to review the publication )

Leukemia, 2017, 31(11):2336-2346

PubMed: 28280274 ( click the link to review the publication )

Cancer Res, 2017, 77(7):1697-1708

PubMed: 28108507 ( click the link to review the publication )

Leuk Lymphoma, 2017, 10.1080/10428194.2017.1289522

PubMed: 28276286 ( click the link to review the publication )

Blood Adv, 2017, 1(20):1635-1644

PubMed: 29296810 ( click the link to review the publication )

Oncotarget, 2017, 8(32):52026-52044

PubMed: 28881711 ( click the link to review the publication )

Blood, 2016, 127(23):2890-902

PubMed: 27099147 ( click the link to review the publication )

Cancer Res, 2016, 76(6):1528-37

PubMed: 26822154 ( click the link to review the publication )
Cancer Res, 2016, 76(5):1214-24

PubMed: 26833125 ( click the link to review the publication )

Sci Rep, 2016, 6:28032

PubMed: 27346558 ( click the link to review the publication )

Ann Hematol, 2016, 95(5):783-91

PubMed: 26891877 ( click the link to review the publication )

PLoS One, 2016, 11(7):e0158290

PubMed: 27387666 ( click the link to review the publication )

Int J Hematol, 2016, 103(1):95-106

PubMed: 26590920 ( click the link to review the publication )

Oncotarget, 2016, 7(31):49786-49799

PubMed: 27391351 ( click the link to review the publication )

Oncotarget, 2016, 7(12):13886-901

PubMed: 26883104 ( click the link to review the publication )

Leukemia, 2015, 29(12):2382-9

PubMed: 26172401 ( click the link to review the publication )

Leukemia, 2015, 29(4):828-38

PubMed: 25322685 ( click the link to review the publication )

Leukemia, 2015, 29(12):2390-2

PubMed: 26108694 ( click the link to review the publication )

Sci Adv, 2015, 1(8):e1500221

PubMed: 26601252 ( click the link to review the publication )

Oncotarget, 2015, 6(35):38061-78

PubMed: 26515730 ( click the link to review the publication )

Blood, 2014, 123(18):2826-37

PubMed: 24668492 ( click the link to review the publication )

Blood, 2014, 123(5):734-42

PubMed: 24282218 ( click the link to review the publication )

Nat Commun, 2014, 5:3672

PubMed: 24739485 ( click the link to review the publication )

Clin Cancer Res, 2014, 20(8):2092-103

PubMed: 24436473 ( click the link to review the publication )

Leukemia, 2014, 28(2):293-301

PubMed: 23748345 ( click the link to review the publication )

Leukemia, 2014, 28(11):2197-205

PubMed: 24699302 ( click the link to review the publication )

Genes Dev, 2014, 28(11):1179-90

PubMed: 24888589 ( click the link to review the publication )

Proc Natl Acad Sci USA, 2014, 10.1073/pnas.1320661111

PubMed: 24623852 ( click the link to review the publication )

Cancer Discov, 2014, 4(2):200-15

PubMed: 24362263 ( click the link to review the publication )

Mol Cancer Ther, 2014, 13(10):2315-27

PubMed: 25053825 ( click the link to review the publication )

J Biol Chem, 2014, 289(45):31053-65

PubMed: 25237195 ( click the link to review the publication )

PLoS One, 2013, 8(9):e74653

PubMed: 24040307 ( click the link to review the publication )
PLoS One, 2013, 8(8): e71266

PubMed: 23967177 ( click the link to review the publication )

Leuk Res, 2013, 37(11):1557-64

PubMed: 23998902 ( click the link to review the publication )

Br J Pharmacol, 2012, 166(3):858-76

PubMed: 22250956 ( click the link to review the publication )

Purity & Quality Control

Choose Selective Target Protein Ligand Inhibitors

Biological Activity

Description

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 K_d 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	Activity Description	PMID
HL60/VCR	MX\GeY5kfGmxbjDBd5NigQ>?	Mm[yNE4yNTFyIN88US=>	Mm\ON\|AhdWmw	MUPlcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI>	NGrmbYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2O\|E4Pyd-MkO5OlcyPzd:L3G+
K562/ABCB1	Ml\sSpVv[3Srb36gRZN{[Xl?	NXe4W4I5OC5zLUGwJO69VQ>?	NI\Wc2Y{OCCvaX6=	NYfaUXF5\W6qYX7j[ZMhfXC2YXvlJI9nKHO3YoP0doF1\XNib3[gRWJETzJiYX7kJGFDS0JzIHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{	NF34NXU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2O\|E4Pyd-MkO5OlcyPzd:L3G+
8226/MR20	NVLrW5l{TnWwY4Tpc44hSXO\|YYm=	NH\EXWcxNjFvMUCg{txO	MojxN\|AhdWmw	MYflcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI>	MmKxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NkexO\|coRjJ\|OU[3NVc4RC:jPh?=
K562/ABCG2	NHWxS5dHfW6ldHnvckBCe3OjeR?=	NHOzc2sxNjFvMUCg{txO	MlH0N\|AhdWmw	MUXlcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI>	NYHPRW5mRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OlcyPzdpPkKzPVY4OTd5PD;hQi=>
MCF-7 FLV1000	NETrXVRMcW6jc3WgRZN{[Xl?	MYGw5qCUOzBiwsXN	NYnJS3dDPSCvaX6=	NITlS4xl\WO{ZXHz[ZMhYzF{NVndMWlCSVBicHjveI9t[WKnbHnu[{Bw\iCDQlPCNUBifCCLQ{WwJI9nKDNwMzFOwG0>	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl4N{G3O{c,OjN7NkexO\|c9N2F-
MCF-7 FLV1000	Mk\xT4lv[XOnIFHzd4F6	MX:w5qCUOzBiwsXN	NHe2T3I2KG2rbh?=	Ml[w[IVkemWjc3XzJHsyOjWLXT3JRWFRKHCqb4TvcIFj\Wyrbnegc4YhSUKFQkKgZZQhUUN3MDDv[kAxNjB5IN88US=>	NVrYZlJ2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OlcyPzdpPkKzPVY4OTd5PD;hQi=>
K562/ABCG2	MVzD[YxtKF[rYXLpcIl1gSCDc4PhfZM>	NVH2e20yOC5zL{CuOU8yKML3TR?=	M3LES\|k3KGh?	MVTz[Y5{cXSrenXzJGs2PjJxQVLDS\|Ih[2WubIOgeI8hdWm2b4jhcpRzd26nIITvdI91\WOjbtMg	M2WyTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OU[3NVc4Lz5{M{m2O\|E4PzxxYU6=
8226/MR20	MXTD[YxtKF[rYXLpcIl1gSCDc4PhfZM>	NHezT5cxNjFiwsXN	MYC5OkBp	NXvDdWhSe2Wwc3n0bZpmeyCNNU[yM2FDS0d{IHPlcIx{KHSxIH3peI95[W62cn;u[UB1d3CxdHXjZY7DqA>?	MnXzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NkexO\|coRjJ\|OU[3NVc4RC:jPh?=
HMC1.1	NGnleoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NXHLbo05UUN3ME2xOEBvVQ>?	Mly5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ\|NEm3N\|E4RC:jPh?=
HMC1.2	MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MoTlTWM2OD1zN{K3JI5O	M{PET\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEm3N\|E4Lz5{M{S5O\|MyPzxxYU6=
p815	MmT5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M1jYN2lEPTB;NES1JI5O	M2K0[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEm3N\|E4Lz5{M{S5O\|MyPzxxYU6=
Kasumi-1	M2Dr[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MVfJR\|UxRTN4IH7N	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
M-07e + SCF	M{SyWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MXfJR\|UxRTd5IH7N	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
EOL-1	M2HxPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M4L1RWlEPTB;MTDuUS=>	NFnYe\|U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
MV4;11	M{Hz[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NHTTT2dKSzVyPDCxJI5O	NUjNdXg2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
MOLM14	NIrSRVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M1XmSGlEPTB:IEGgcm0>	Mli5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ\|NEm3N\|E4RC:jPh?=
Pat.221	MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MUfJR\|UxRTZ5NTDuUS=>	M1LtbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEm3N\|E4Lz5{M{S5O\|MyPzxxYU6=
Pat.279	M1X2UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MoS3TWM2OD1\|NEO0JI5O	NFz5V4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
Pat.299	NGTz[\|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M2m2XmlEPTB;N{K0PEBvVQ>?	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
Pat.305	MkjpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NX\iVY9{UUN3ME23NFc6KG6P	NUjDc4J7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
Pat.375	NHjYWFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M1qxfGlEPTB;NUCzJI5O	NGLvSII9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
Pat.379	NIHjNFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MWLJR\|UxRThyNjDuUS=>	NVrjXo55RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
Pat.368	MlPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M{LDUGlEPTB;MkewNEBvVQ>?	NEC4U2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
Pat.601	NGfKe5FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MWfJR\|UxRTFzNUOgcm0>	NXvXeY9SRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
HMC1.1	M4nF[WFxd3C2b4Ppd{BCe3OjeR?=			NHeyR4hKSzVyPUOxJI5O	MlLiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ\|NEm3N\|E4RC:jPh?=
p815	NFTZVFZCeG:ydH;zbZMhSXO\|YYm=			M4S0fmlEPTB;M{SxJI5O	NGrGSZg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
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MV4-11	MoC4RZBweHSxc3nzJGF{e2G7		M3;WXVgwOjRiaB?=	MkjHbY5lfWOnczDzbYdvcW[rY3HueEBidmRiZH;z[U1l\XCnbnTlcpQhWEGUUDDjcIVifmGpZTDhcoQh[WOldX31cIF1cW:wIH;mJJN2[i1{TjDEUmE>	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzRzMkmzNUc,OjN2MUK5N\|E9N2F-
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AML	NXnWcYhKS3m2b4TvfIlkcXS7IHHzd4F6			NEPrTWNEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCVUxiY3XscJMhcXOxbHH0[YQh\nKxbTDy[YxieHOnZDDhZ5V1\SCveXXsc4llKGyndXvlcYliKHCjdHnlcpQhcGG{Yn;ybY5oKE[OVEOgTXRFKG23dHH0bY9vKGK7IF3UWEBie3OjeTygTWM2OCB;IECuNFAxOyEQvF2u	NYX5TIFDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm2OVQ1ODhpPkG5OlU1PDB6PD;hQi=>
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AML	MXPGeY5kfGmxbjDhd5NigQ>?			MnexTY5pcWKrdHnvckBw\iCITGSzJIF2fG:yaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hSU2OIHPlcIx{KGm\|b3zheIVlKG[{b32gdoVt[XC\|ZXSgZYN2fGVibYnlcI9q\CCuZYXr[Y1q[SCyYYTp[Y51KGK7IGfld5Rmem5iYnzveJRqdmduIFnDOVAhRSByLkCwNkDPxE1w	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTZ3NESwPEc,OTl4NUS0NFg9N2F-
RS4-11	NGTXR5FHfW6ldHnvckBie3OjeR?=		NHTCR4QzKGi{cx?=	M3jzPGlvcGmkaYTpc44hd2ZiRlzUN{BifXSxcHjvd5Bpd3K7bHH0bY9vKGmwIHj1cYFvKFKVND2xNUBk\WyuczDh[pRmeiB{IHjyd{BjgSCnbHXjeJJw[2inbXnseY1qdmW\|Y3XuZ4Uh[XO\|YYmsJGlEPTBiPTCwMlAxPDJizszNMi=>	MlLnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl4NUS0NFgoRjF7NkW0OFA5RC:jPh?=
MV4-11	NHizR2RCdnSrdIXtc5Ih[XO\|YYm=	M4LhflExKG2pL3vn	NV;hfVUxPjBiZHH5dy=>	M{HGOWFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3WOE0yOSClZXzsd{B5\W6xZ4Lh[pRm\CCvb4Xz[UBud2SnbDDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIIT1cY9zKHKnZ4Lve5RpKGG2IHH0JFExKG2pL3vnMEBxdyB4MDDkZZl{KHCxc4SgeJJm[XSvZX70	NYPjT4FiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm2OVQ1ODhpPkG5OlU1PDB6PD;hQi=>
MV4-11	MVnBcpRqfHWvb4KgZZN{[Xl?	M2nnNlEhdWdxa3ev[IF6	NY[wUZlQOzBiZHH5dy=>	NWPnSFhVSW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gUXY1NTFzIHPlcIx{KHinbn;ndoFnfGWmIH3veZNmKGKxbnWgcYFzem:5IHXu[5Ji\nSvZX70JI1w\GWuIHHzd4V{e2WmIHHzJIlv[3KnYYPlJI1wfXOnIHzp[oUhe3CjbjDheEAyKG2pL3vnM4RigSxicH:g[o9zKDNyIHThfZMhdWWjc4Xy[YQhd25iZHH5JFc4KHCxc4Sg[I9{\Q>?	M4nHfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NkW0OFA5Lz5zOU[1OFQxQDxxYU6=
MV4-11	M4r2VmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NFHH[4w4OiCqcoO=	M4n5fmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTW[0MVEyKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDj[YxtKHSrdHXyMYJtfWViY3XscEB3cWGkaXzpeJkh[XO\|YYmsJGlEPTBiPTCwMlAxODV4IN88UU4>	M4TwNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7N{W0NVk6Lz5zOUe1OFE6QTxxYU6=
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MV4-11	MVnBcpRqfHWvb4KgZZN{[Xl?	Mk\WNUBu\y:tZx?=	NYP6cGVDOjhiZHH5dy=>	M4fOZmFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3WOE0yOSClZXzsd{B5\W6xZ4Lh[pRm\CCrbjDheIh6dWmlIH71[IUhdW:3c3WgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjD0eY1weiCpcn;3eIgh[XRiMTDt[{9s\yxicH:gVWQh\m:{IEK4JIRigXNibXXhd5Vz\WRiZIXybY5oKGSxc3nu[{Bx\XKrb3S=	NIrke3U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUe1OFE6QSd-MUm3OVQyQTl:L3G+
MV4-11	M1;XeWFvfGm2dX3vdkBie3OjeR?=	M1PpblMhdWdxa3e=	MnP3Nlgh\GG7cx?=	MVrBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPVkStNVEh[2WubIOgfIVvd2e{YX\0[YQhcW5iYYTofY1q[yCwdXTlJI1wfXOnIHHzd4V{e2WmIHHzJJR2dW:{IHfyc5d1cCC{ZXfy[ZN{cW:wIHH0JFMhdWdxa3esJJBwKFGGIH\vdkAzQCCmYYnzJI1m[XO3cnXkJIFnfGW{IHTvd4lv\yCyZYLpc4Q>	NVqxW3h3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm3OVQyQTlpPkG5O\|U1OTl7PD;hQi=>
MV4-11	M4rKNWFvfGm2dX3vdkBie3OjeR?=	MX2xNEBu\y:tZx?=	NI\6ZWczQCCmYYnz	MU\BcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPVkStNVEh[2WubIOgfIVvd2e{YX\0[YQhcW5iYYTofY1q[yCwdXTlJI1wfXOnIHHzd4V{e2WmIHHzJJR2dW:{IHfyc5d1cCC{ZXfy[ZN{cW:wIHH0JFExKG2pL3vnMEBxdyCTRDDmc5IhOjhiZHH5d{Bu\WG\|dYLl[EBi\nSncjDkc5NqdmdicHXybY9l	NF36Rng9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUe1OFE6QSd-MUm3OVQyQTl:L3G+
MV4-11	NUfFSYxzSW62aYT1cY9zKGG\|c3H5	MmO4N{Bu\y:tZx?=	NH3QNZUzQCCmYYnz	NXToNGx[SW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gUXY1NTFzIHPlcIx{KHinbn;ndoFnfGWmIHnuJIF1cHmvaXOgcpVl\SCvb4Xz[UBie3Onc4Pl[EBieyC\|dYDwdoV{e2mxbjDv[kB1fW2xcjD2c4x2dWViYYSgN{Bu\y:tZzygdI8hWURiZn;yJFI5KGSjeYOgcYVie3W{ZXSgZYZ1\XJiZH;zbY5oKHCncnnv[C=>	NVXvOmx5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm3OVQyQTlpPkG5O\|U1OTl7PD;hQi=>
MV4-11	M2XqT2FvfGm2dX3vdkBie3OjeR?=	MlHPNVAhdWdxa3e=	MVWyPEBl[Xm\|	NIm0V5BCdnSrdIXtc5Ih[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNWlQuOTFiY3XscJMhgGWwb3fyZYZ1\WRiaX6gZZRpgW2rYzDueYRmKG2xdYPlJIF{e2W\|c3XkJIF{KHO3cIDy[ZN{cW:wIH;mJJR2dW:{II\vcJVu\SCjdDCxNEBu\y:tZzygdI8hWURiZn;yJFI5KGSjeYOgcYVie3W{ZXSgZYZ1\XJiZH;zbY5oKHCncnnv[C=>	Mnn4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl5NUSxPVkoRjF7N{W0NVk6RC:jPh?=
MV4-11	NIXYNXhCdnSrdIXtc5Ih[XO\|YYm=	NHS0[VkyOCCvZz;r[y=>	M37l[VI5KGSjeYO=	M3rxSWFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3WOE0yOSClZXzsd{B5\W6xZ4Lh[pRm\CCrbjDheIh6dWmlIH71[IUhdW:3c3WgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjD0eY1weiCpcn;3eIgh[XRiMUCgcYcwc2duIIDvJHFFKG[xcjCyPEBl[Xm\|IH3lZZN2emWmIHHmeIVzKDN{IHThfZMheG:\|dHTvd4U>	M3XUU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7N{W0NVk6Lz5zOUe1OFE6QTxxYU6=
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MV4-11	M3G3WGFvfGm2dX3vdkBie3OjeR?=	Mly4NVAhdWdxa3e=	MY[0PEBl[Xm\|	MUjBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPVkStNVEh[2WubIOgfIVvd2e{YX\0[YQhcW5iboXk[UBud3W\|ZTDhd5Nme3OnZDDhd{B1fW2xcjDy[Ydz\XO\|aX;uJIF1KDFyIH3nM4toNCCybzDx[EBi\G2rbnnzeIVz\WRib36g[IF6KDhidH:gNVIhdWWjc4Xy[YQh\HW{aX7nJFQ5KGSjeYOgdI9{fCCuYYP0JIRwe2V?	NF3FVlE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NVAzOyd-Mk[wPFExOjN:L3G+
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MV4-11	M1\VPGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NEi1eVE1QCCqcoO=	NHm5R\|BIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBOXjRvMUGgZ4VtdHNiZYjwdoV{e2mwZzDGUHQ{NUmWRDDh[pRmeiB2ODDodpMh[nliWGTUJIF{e2G7LDDHTVUxKD1iMT6xNFMh\|ryPLh?=	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzF6N{i2NEc,OjdzOEe4OlA9N2F-
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MOLM13	M33sWmFxd3C2b4Ppd{Bie3OjeR?=	NETJ[mYyODBibl2=	MlPDNVIhcHK\|	M4jv[Glv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gbJVu[W5iTV;MUVE{KGOnbHzzJIF{e2W\|c3XkJIF{KGOuZXH2ZYdmKG:oIGDBVnAh[XRiMUCwJI5OKGGodHXyJFEzKGi{czDifUBqdW23bn;icI91fGmwZzDt[ZRpd2R?	MknuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh7NU[5NlMoRjJ6OUW2PVI{RC:jPh?=
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MOLM13	MVfBdI9xfG:\|aYOgZZN{[Xl?	M{TleVExOCCwTR?=	NGfqdGQyOiCqcoO=	MYPJcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKE2RTF2xN{Bk\WyuczDhd5Nme3OnZDDhd{BkdGWjdnHn[UBw\iClYYPwZZNmNTNiYYSgNVAxKG6PIHHmeIVzKDF{IHjyd{BjgSCrbX31co9jdG:2dHnu[{Bu\XSqb3S=	MlvUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh7NU[5NlMoRjJ6OUW2PVI{RC:jPh?=
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MV4-11	MWLBdI9xfG:\|aYOgZZN{[Xl?	NYewWGdkOTByIH7N	NUTob5dIPDhiaILz	MnnTTY5lfWO2aX;uJI9nKGGyb4D0c5NqeyCrbjDoeY1idiCPVkStNVEh[2WubIOgZZN{\XO\|ZXSgZZMh[2ynYY\h[4Uhd2ZiY3HzdIF{\S1\|IHH0JFExOCCwTTDh[pRmeiB2ODDodpMh[nliaX3teY5w[myxdITpcochdWW2aH;k	MkDIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh7NU[5NlMoRjJ6OUW2PVI{RC:jPh?=
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BT-12	NV35RnFNeUiWUzDhd5NigQ>?			M1vFSJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGJVNTF{IHPlcIx{	NG\aRZk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
LAN-5	NEPKPIpyUFSVIHHzd4F6			M4O1PJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGxCVi13IHPlcIx{	M2WxclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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A673	NHryfVRyUFSVIHHzd4F6			NXHqSIxFeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhSTZ5MzDj[Yxteyl?	MkfUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
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SJ-GBM2	NGmwVYxyUFSVIHHzd4F6			MkTpdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgV2ouT0KPMjDj[Yxtew>?	NH6wVmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
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MV4-11	M160Nmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NEjydJk4OiCqcoO=	M4SzT2dzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJG1XPC1zMTDj[YxteyCjZoTldkA4OiCqcoOgZpkh[2GuY3XpckBCVSCmeXWtZoF{\WRiZnz1c5Jme2OnbnPlJIF{e2G7LDDHTVUxKD1iMD6wNFMh\|ryPLh?=	NIHS[nc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[3NlA1QSd-Mkm2O\|IxPDl:L3G+
BA/F3	NX\jcHNkTnWwY4Tpc44h[XO\|YYm=		NXGxd2RYPzJiaILz	NUL3UYZnUW6qaXLpeIlwdiCxZjDGUHQ{KEmWRDDteZRidnRiKIXub45wf25ib4Lp[4lvMSC2cnHud4Zm[3SnZDDpckBud3W\|ZTDCRU9HOyClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkA4OiCqcoOgZpkh[2GuY3XpckBCVSCmeXWtZoF{\WRiZnz1c5Jme2OnbnPlJIF{e2G7LDDHTVUxKD1iMD6wNFch\|ryPLh?=	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ5MkC0PUc,Ojl4N{KwOFk9N2F-
Sf9	MoXTSpVv[3Srb36gZZN{[Xl?			M{j4c2lvcGmkaYTpc44hd2ZiTj30[ZJucW6jbDDHV3QwUGm\|Nj3meZNm\CC{ZXPvcYJqdmGwdDDoeY1idiCITGSzJEhTPTdzIITvJHM6QTNicnXzbYR2\XNrIFnUSEBufXSjboSg[ZhxemW\|c3XkJIlvKFOoOTDpcpNm[3RiY3XscJMhfXOrbnegdI9tgSBqQXzhMGdtfSyOeYOsWJlzMSB4OkK6OVoyKGi7ZILvZpJwdWmmZTDhd{B{fWK\|dILheIUhcW5icILld4Vv[2Vib3[gX4didW2jLUOzVH1CXFBuIFnDOVAhRSByLkCxJO69VS5?	NYL0XoQzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2O\|IxPDlpPkK5OlczODR7PD;hQi=>
Sf9	NUn0TW8{TnWwY4Tpc44h[XO\|YYm=			M3r1U2lvcGmkaYTpc44hd2ZiTj30[ZJucW6jbDDHV3QwUGm\|Nj3meZNm\CC{ZXPvcYJqdmGwdDD3bYxlKHS7cHWgbJVu[W5iRlzUN{ApWjV5MTD0c{BUQTl\|IILld4llfWW\|KTDlfJBz\XO\|ZXSgbY4hW2Z7IHnud4VkfCClZXzsd{B2e2mwZzDwc4x6KCiDbHGsS4x2NEy7czzUfZIqKDZ8Mkq1PlEhcHmmcn;ido9ucWSnIHHzJJN2[nO2cnH0[UBqdiCycnXz[Y5k\SCxZjDb[4FudWFvM{PQYWFVWCxiSVO1NEA:KDBwMEO2JO69VS5?	NWH4RpA3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2O\|IxPDlpPkK5OlczODR7PD;hQi=>
Kasumi-1	NVL6SIlKT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		NUHKVItWPzJiaILz	NEXydVhIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBM[XO3bXmtNUBk\WyuczDh[pRmeiB5MjDodpMh[nliY3HsZ4VqdiCDTTDkfYUu[mG\|ZXSg[ox2d3Knc3PlcoNmKGG\|c3H5MEBIUTVyIE2gNE4xPjRizszNMi=>	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ5MkC0PUc,Ojl4N{KwOFk9N2F-
Sf9	Mk\ISpVv[3Srb36gZZN{[Xl?			NH7EZ4pKdmirYnn0bY9vKG:oIF6teIVzdWmwYXygS3NVN0irc{[t[pV{\WRicnXjc41jcW6jboSgbJVu[W5iRlzUN{ApWjV5MTD0c{BUQTl\|IILld4llfWW\|KTDEPFM2YSCvdYThcpQh\XiycnXzd4VlKGmwIGPmPUBqdnOnY4SgZ4VtdHNidYPpcocheG:ueTCoRYxiNEeudTzMfZMtXHm{KTC2PlI7PTpzIHj5[JJw[nKxbXnk[UBieyC\|dXLzeJJifGViaX6gdJJme2WwY3Wgc4YhY2ejbX3hMVM{WF2DVGCsJGlEPTBiPTCwMlE{PiEQvF2u	Mn7ZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl4N{KwOFkoRjJ7NkeyNFQ6RC:jPh?=
BA/F3	MnXUS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		NHfBdXk4OiCqcoO=	NXryb4d6T3Kxd4ToJIlvcGmkaYTpc44hd2ZibX;1d4UhSkFxRkOgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KGOjbHPlbY4hSU1iZInlMYJie2WmIH\seY9z\XOlZX7j[UBie3OjeTygS2k2OCB;IEGuOFUzKM7:TT6=	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ5MkC0PUc,Ojl4N{KwOFk9N2F-
MV4-11	NUeySGVLTnWwY4Tpc44h[XO\|YYm=	MV[wMlAyKHSxIEGwNEBvVQ>?	M2PhclEhcHJ?	NF;5UmtKdmirYnn0bY9vKG:oIF\MWFMhUVSGIH31eIFvfCCrbjDoeY1idiCPVkStNVEh[2WubIOgZZN{\XO\|ZXSgZZMh\GWlcnXhd4UhcW5iQVvUJJBpd3OyaH;yfYxifGmxbjDheEBUPDd\|IHH0JFAvODFidH:gNVAxKG6PIHHmeIVzKDFiaIKgZpkhcW2vdX7vZoxwfCCjbnHsfZNqew>?	NVzCXFBmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2O\|IxPDlpPkK5OlczODR7PD;hQi=>
MV4-11	MXLGeY5kfGmxbjDhd5NigQ>?	MVuwMlAyKHSxIEGwNEBvVQ>?	MWexJIhz	NITR[XNKdmirYnn0bY9vKG:oIF\MWFMhUVSGIH31eIFvfCCrbjDoeY1idiCPVkStNVEh[2WubIOgZZN{\XO\|ZXSgZZMh\GWlcnXhd4UhcW5iTVXLNU8zKHCqb4PwbI9zgWyjdHnvckBifCCVMkG3M\|IzOSCjdDCwMlAyKHSxIEGwNEBvVSCjZoTldkAyKGi{IHL5JIludXWwb3Lsc5Qh[W6jbInzbZM>	NIfPSYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[3NlA1QSd-Mkm2O\|IxPDl:L3G+
MV4-11	NX:ybFNYTnWwY4Tpc44h[XO\|YYm=	NVrsTVRoOSCwTR?=	MnHRNUBpeg>?	M4jMbmlvcGmkaYTpc44hd2ZiRlzUN{BKXERibYX0ZY51KGG3dH;wbI9{eGixconsZZRqd25iYYSgXVU5QS93OUGgbY4hcHWvYX6gUXY1NTFzIHPlcIx{KGG2IEGgcm0h[W[2ZYKgNUBpeiCkeTDpcY12dm:kbH;0JIFv[Wy7c3nz	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ5MkC0PUc,Ojl4N{KwOFk9N2F-
MV4-11	MXnGeY5kfGmxbjDhd5NigQ>?	NXPFUmhLOSCwTR?=	MlX6NUBpeg>?	NEDUUXVKdmirYnn0bY9vKG:oIF\MWFMhUVSGIH31eIFvfCCjdYTvdIhwe3Cqb4L5cIF1cW:wIHH0JHk5PDJiaX6gbJVu[W5iTW[0MVEyKGOnbHzzJIF1KDFibl2gZYZ1\XJiMTDodkBjgSCrbX31co9jdG:2IHHuZYx6e2m\|	NXXwcoczRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2O\|IxPDlpPkK5OlczODR7PD;hQi=>
MV4-11	NXvXbYdnTnWwY4Tpc44h[XO\|YYm=	NG\SZVAxNjBzIITvJFExOCCwTR?=	MV[xJIhz	MXjJcohq[mm2aX;uJI9nKE[OVEOgTXRFKG23dHHueEBqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4hW1SDVEWgdIhwe3Cqb4L5cIF1cW:wIHH0JHk3QTRiYYSgNE4xOSC2bzCxNFAhdk1iYX\0[ZIhOSCqcjDifUBqdW23bn;icI91KGGwYXz5d4l{	NVzwNFBSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2O\|IxPDlpPkK5OlczODR7PD;hQi=>
MV4-11	MYDGeY5kfGmxbjDhd5NigQ>?	M3[xSlAvODFidH:gNVAxKG6P	M2XHVlEhcHJ?	NHz5fotKdmirYnn0bY9vKG:oIF\MWFMhUVSGIH31eIFvfCCrbjDoeY1idiCPVkStNVEh[2WubIOgZZN{\XO\|ZXSgZZMh\GWlcnXhd4UhcW5iRWLLNU8zKHCqb4PwbI9zgWyjdHnvckBifCCWMkCyM3kzODRiYYSgNE4xOSC2bzCxNFAhdk1iYX\0[ZIhOSCqcjDifUBqdW23bn;icI91KGGwYXz5d4l{	NX7HUnJ4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2O\|IxPDlpPkK5OlczODR7PD;hQi=>
MV4-11	MmHPSpVv[3Srb36gZZN{[Xl?	MV2xNEBu\y:tZx?=	NFLPPY4zPCCqcoO=	NF:4W3BKdiC4aY\vJIlvcGmkaYTpc44hd2ZiRlzUN{BKXERibYX0ZY51KGmwIHj1cYFvKE2YND2xNUBk\WyuczD4[Y5w\3KjZoTl[EBqdiCjdHj5cYlkKG63L371JI1wfXOnIHHzd4V{e2WmIHHzJIRm[3KnYYPlJIlvKFOWQWS1JJBpd3OyaH;yfYxifGmxbjDheEB[Pjl2IHH0JFExKG2pL3vnMEBqeCCjZoTldkAzPCCqcoOgZpkhcW2vdX7vZoxwfCCvZYToc4QhemWuYYTpeoUhfG9iY3;ueJJwdA>?	NHvvfZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[3NlA1QSd-Mkm2O\|IxPDl:L3G+
MV4-11	M3fhSmZ2dmO2aX;uJIF{e2G7	MXqwMlEhfU1?	M1Pm[lQhcHK\|	M{DHcWlvcGmkaYTpc44hd2ZiRlzUN{BqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKEGNVDDwbI9{eGixconsZZRqd25iYYSgV4VzPDd\|IILld4llfWViYYSgNE4yKHWPIHHmeIVzKDRiaILzJIJ6KFenc4Tldo4h[myxdDDhcoFtgXOrcx?=	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTh7NEm0OEc,Ojl6OUS5OFQ9N2F-
MV4-11	MmS1SpVv[3Srb36gZZN{[Xl?	M2fYc\|AvOSC3TR?=	M{XnSVQhcHK\|	MmTlTY5pcWKrdHnvckBw\iCITGSzJIlvKGi3bXHuJG1XPC1zMTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hW1SDVEWgdIhwe3Cqb4L5cIF1cW:wIHH0JHR6ejZ7NDDy[ZNq\HWnIHH0JFAvOSC3TTDh[pRmeiB2IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm\|aYO=	NH3zWXk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUi5OFk1PCd-Mkm4PVQ6PDR:L3G+
MV4-11	MnjySpVv[3Srb36gZZN{[Xl?	NU\FclZFOC5zIIXN	NVTNZnM5PCCqcoO=	MXvJcohq[mm2aX;uJI9nKE[OVEOgbY4hcHWvYX6gUXY1NTFzIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBGWktzL{KgdIhwe3Cqb4L5cIF1cW:wIHH0JHRpejJyMj;UfZIzODRicnXzbYR2\XNiYYSgNE4yKHWPIHHmeIVzKDRiaILzJIJ6KFenc4Tldo4h[myxdDDhcoFtgXOrcx?=	NXG5U4tbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm4PVQ6PDRpPkK5PFk1QTR2PD;hQi=>
MV4-11	NIjncHhHfW6ldHnvckBie3OjeR?=	MXywMlEhfU1?	MWK0JIhzew>?	NVTTdG97UW6qaXLpeIlwdiCxZjDGUHQ{KHCqb4PwbI9zgWyjdHnvckBifCCWeYK1PFkwPTlzIILld4llfWW\|IHnuJIh2dWGwIF3WOE0yOSClZXzsd{BifCByLkGgeW0h[W[2ZYKgOEBpenNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{	NEW4b3E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUi5OFk1PCd-Mkm4PVQ6PDR:L3G+

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	phospho-FLT3 / FLT3; PubMed: 22875611 Haematologica (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 Cancer Res 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 Leukemia 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 PLoS One 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]	- Collapse 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]	- Collapse 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]	- Collapse 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)

References

[1] Zarrinkar PP, et al. Blood, 2009, 114(14), 2984-2992.

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 Download Quizartinib (AC220) SDF

Molecular Weight	560.67
Formula	C₂₉H₃₂N₆O₄S
CAS No.	950769-58-1
Storage	3 years-20°C powder 2 years-80°C 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

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Working concentration： mg/ml；

Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take μL DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-09-06)

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

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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.

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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.

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Quizartinib (AC220)