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Quizartinib (AC220)

Name: Quizartinib (AC220)
Brand: Selleck Chemicals
SKU: S1526
Rating: 5 (105 reviews)

Catalog No.S1526

For research use only.

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.

CAS No. 950769-58-1

Selleck's Quizartinib (AC220) has been cited by 105 publications

Purity & Quality Control

Choose Selective Target Protein Ligand Inhibitors

Related Compound Libraries

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	Formulation	Activity Description	PMID

HL60/VCR	NYPu[2J{TnWwY4Tpc44hSXO\|YYm=	NVLkXpluOC5zLUGwJO69VQ>?	M1rqbVMxKG2rbh?=	M2rIbYVvcGGwY3XzJJVxfGGtZTDv[kB{fWK\|dILheIV{KG:oIFHCR2czKGGwZDDBRmNDOSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>?	NGryTpQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2O\|E4Pyd-MkO5OlcyPzd:L3G+
K562/ABCB1	MnyySpVv[3Srb36gRZN{[Xl?	NGDWR5UxNjFvMUCg{txO	MUizNEBucW5?	MXzlcohidmOnczD1dJRic2Vib3[gd5Vje3S{YYTld{Bw\iCDQlPHNkBidmRiQVLDRlEhcW5iYTDjc45k\W62cnH0bY9vNWSncHXu[IVvfCCvYX7u[ZI>	MkDkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NkexO\|coRjJ\|OU[3NVc4RC:jPh?=
8226/MR20	NX;GUmxjTnWwY4Tpc44hSXO\|YYm=	Mn3KNE4yNTFyIN88US=>	NXHQTnlKOzBibXnu	M3XYdoVvcGGwY3XzJJVxfGGtZTDv[kB{fWK\|dILheIV{KG:oIFHCR2czKGGwZDDBRmNDOSCrbjDhJINwdmOnboTyZZRqd25vZHXw[Y5l\W62IH3hco5meg>?	NWrDTnYyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OlcyPzdpPkKzPVY4OTd5PD;hQi=>
K562/ABCG2	MYfGeY5kfGmxbjDBd5NigQ>?	MVuwMlEuOTBizszN	NYLhZnBlOzBibXnu	NUnOO3Jm\W6qYX7j[ZMhfXC2YXvlJI9nKHO3YoP0doF1\XNib3[gRWJETzJiYX7kJGFDS0JzIHnuJIEh[2:wY3XueJJifGmxbj3k[ZBmdmSnboSgcYFvdmW{	NG\TPWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m2O\|E4Pyd-MkO5OlcyPzd:L3G+
MCF-7 FLV1000	M2rMSmtqdmG\|ZTDBd5NigQ>?	NEHBOIQx6oDVM{CgxtVO	NUfB[ZBRPSCvaX6=	MnPU[IVkemWjc3XzJHsyOjWLXT3JRWFRKHCqb4TvcIFj\Wyrbnegc4YhSUKFQkGgZZQhUUN3MDDv[kA{NjNizszN	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl4N{G3O{c,OjN7NkexO\|c9N2F-
MCF-7 FLV1000	NFHxXJZMcW6jc3WgRZN{[Xl?	NFr5VpMx6oDVM{CgxtVO	NHLSdmY2KG2rbh?=	M{PLT4Rm[3KnYYPld{BcOTJ3SW2tTWFCWCCyaH;0c4xi[mWuaX7nJI9nKEGEQ1KyJIF1KEmFNUCgc4YhOC5yNzFOwG0>	MoPVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NkexO\|coRjJ\|OU[3NVc4RC:jPh?=
K562/ABCG2	NGLpZ4dE\WyuIG\pZYJqdGm2eTDBd5NigXN?	MkXkNE4yNzBwNT:xJOK2VQ>?	M2rYPFk3KGh?	NUXK[oVke2Wwc3n0bZpmeyCNNU[yM2FDS0d{IHPlcIx{KHSxIH3peI95[W62cn;u[UB1d3CxdHXjZY7DqA>?	M1iwXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OU[3NVc4Lz5{M{m2O\|E4PzxxYU6=
8226/MR20	MYLD[YxtKF[rYXLpcIl1gSCDc4PhfZM>	MYWwMlEhyrWP	M1XmT\|k3KGh?	MnjTd4Vve2m2aYrld{BMPTZ{L1HCR2czKGOnbHzzJJRwKG2rdH;4ZY51em:wZTD0c5BwfGWlYX9CpC=>	MkP0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NkexO\|coRjJ\|OU[3NVc4RC:jPh?=
HMC1.1	NU\PbZYzT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NHHXU2NKSzVyPUG0JI5O	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
HMC1.2	NYWxZXZ6T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M{LSXGlEPTB;MUeyO{BvVQ>?	NWLz[4lKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
p815	MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MlrnTWM2OD12NEWgcm0>	NG\NblA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
Kasumi-1	MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NIPqc3VKSzVyPUO2JI5O	Mo\yQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ\|NEm3N\|E4RC:jPh?=
M-07e + SCF	MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MojpTWM2OD15NzDuUS=>	NWm1[3RIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
EOL-1	NFnWfI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MlHkTWM2OD1zIH7N	MkXiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ\|NEm3N\|E4RC:jPh?=
MV4;11	MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M3vPVGlEPTB:IEGgcm0>	NU\MN4I1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
MOLM14	NI\WWmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NXXVTXB{UUN3MEygNUBvVQ>?	M2rIZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEm3N\|E4Lz5{M{S5O\|MyPzxxYU6=
Pat.221	MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MXTJR\|UxRTZ5NTDuUS=>	NH;6fnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
Pat.279	MnThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MV7JR\|UxRTN2M{Sgcm0>	M36w[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEm3N\|E4Lz5{M{S5O\|MyPzxxYU6=
Pat.299	NV;zUXRWT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NY\pbXgyUUN3ME23NlQ5KG6P	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
Pat.305	NFSwOYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MlTVTWM2OD15MEe5JI5O	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
Pat.375	MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M3vUd2lEPTB;NUCzJI5O	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
Pat.379	M3rQOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NVnIWWVyUUN3ME24NFYhdk1?	MmLBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ\|NEm3N\|E4RC:jPh?=
Pat.368	Mn7PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NIWxUmRKSzVyPUK3NFAhdk1?	M3y2R\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEm3N\|E4Lz5{M{S5O\|MyPzxxYU6=
Pat.601	NYjSSVM2T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MULJR\|UxRTFzNUOgcm0>	MlmzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ\|NEm3N\|E4RC:jPh?=
HMC1.1	MUfBdI9xfG:\|aYOgRZN{[Xl?			NUPNUnJjUUN3ME2zNUBvVQ>?	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
p815	MV\BdI9xfG:\|aYOgRZN{[Xl?			MoW5TWM2OD1\|NEGgcm0>	NWnNUIExRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
Kasumi-1	NXzSb4JHSXCxcITvd4l{KEG\|c3H5			M1H5UmlEPTB;Nkegcm0>	MmXmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OUezNVcoRjJ\|NEm3N\|E4RC:jPh?=
M-07e + SCF	NVflSm5FSXCxcITvd4l{KEG\|c3H5			MXjJR\|UxRTd6IH7N	NFPlRWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
EOL-1	NVfDXIprSXCxcITvd4l{KEG\|c3H5			MVXJR\|UxRCBzIH7N	M{nMfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEm3N\|E4Lz5{M{S5O\|MyPzxxYU6=
MV4;11	NETEWnJCeG:ydH;zbZMhSXO\|YYm=			M2D6N2lEPTB;MjDuUS=>	NW\ObHdIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
MOLM14	MXzBdI9xfG:\|aYOgRZN{[Xl?			M3THSWlEPTB;MzDuUS=>	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR7N{OxO{c,OjN2OUezNVc9N2F-
GIST822	MljxRZBweHSxc3nzJGF{e2G7			MVrJR\|UxRTFyOTDuUS=>	NVS4Zos3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PVc{OTdpPkKzOFk4OzF5PD;hQi=>
Pat.368	M13LWWFxd3C2b4Ppd{BCe3OjeR?=			NEDPOXNKSzVyPUK5PVghdk1?	M4LMdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEm3N\|E4Lz5{M{S5O\|MyPzxxYU6=
Pat.601	MkD1RZBweHSxc3nzJGF{e2G7			NUHxWZBMUUN3ME24O\|Yhdk1?	NFzRUIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S5O\|MyPyd-MkO0PVc{OTd:L3G+
MV4-11	M{WwZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7		M1TMbFczKGh?	MkfITWM2OD1yLkOgcm0>	NXHJUZhORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0NVI6OzFpPkKzOFEzQTNzPD;hQi=>
MOLM-14	NWG0NFNPT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MXO3NkBp	NVXhdnVqUUN3ME2wMlEhdk1?	M1rhcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEGyPVMyLz5{M{SxNlk{OTxxYU6=
SEM-K2	NWewVIlJT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MkfsO\|IhcA>?	NV3Sb2FrUUN3ME2wMlQhdk1?	MnnNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2MUK5N\|EoRjJ\|NEGyPVMyRC:jPh?=
RS4;11	NHjnPIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		Ml3YO\|IhcA>?	M2fYOmlEPTB-MUCsNFAxKG6P	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzRzMkmzNUc,OjN2MUK5N\|E9N2F-
THP-1	M3zWcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		M1jmbVczKGh?	MYjJR\|UxRjFyLECwNEBvVQ>?	NFTrfJE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{SxNlk{OSd-MkO0NVI6OzF:L3G+
MV4-11	NUX1dGRzSXCxcITvd4l{KEG\|c3H5		MmHwPE8zPCCq	MmX0bY5lfWOnczDzbYdvcW[rY3HueEBidmRiZH;z[U1l\XCnbnTlcpQhWEGUUDDjcIVifmGpZTDhcoQh[WOldX31cIF1cW:wIH;mJJN2[i1{TjDEUmE>	NGHrWpg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{SxNlk{OSd-MkO0NVI6OzF:L3G+
MOLM-14	NGnpdZdCeG:ydH;zbZMhSXO\|YYm=		NETRWJM5NzJ2IHi=	MlXwbY5lfWOnczDzbYdvcW[rY3HueEBidmRiZH;z[U1l\XCnbnTlcpQhWEGUUDDjcIVifmGpZTDhcoQh[WOldX31cIF1cW:wIH;mJJN2[i1{TjDEUmE>	M2[zWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEGyPVMyLz5{M{SxNlk{OTxxYU6=
SEM-K2	MV;BdI9xfG:\|aYOgRZN{[Xl?		NIHaWHo5NzJ2IHi=	MWfpcoR2[2W\|IIPp[45q\mmlYX70JIFv\CCmb4PlMYRmeGWwZHXueEBRSVKSIHPs[YF3[WenIHHu[EBi[2O3bYXsZZRqd25ib3[gd5VjNTKQIFTORS=>	NInz[II9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{SxNlk{OSd-MkO0NVI6OzF:L3G+
AML	NIjKfmtEgXSxdH;4bYNqfHliYYPzZZk>			NGexS45EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBCVUxiY3XscJMhcXOxbHH0[YQh\nKxbTDy[YxieHOnZDDhZ5V1\SCveXXsc4llKGyndXvlcYliKHCjdHnlcpQhcGG{Yn;ybY5oKE[OVEOgTXRFKG23dHH0bY9vKGK7IF3UWEBie3OjeTygTWM2OCB;IECuNFAxOyEQvF2u	NEPR[Vk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOU[1OFQxQCd-MUm2OVQ1ODh:L3G+
MV4-11	M{LyXGN6fG:2b4jpZ4l1gSCjc4PhfS=>		MlnaO\|IhcHK\|	NITiO4JEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOXjRvMUGgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KGOnbHygeIl1\XJvYnz1[UBie3OjeTygTWM2OCB;IECuNFAxPTZizszNMi=>	NIrBXWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOU[1OFQxQCd-MUm2OVQ1ODh:L3G+
blast cells	MV3GeY5kfGmxbjDhd5NigQ>?		MkjQNkBpenN?	MorTTY5pcWKrdHnvckBw\iCITGSzJGlVTCCvdYThcpQh[XW2b4Doc5NxcG:{eXzheIlwdiCrbjDoeY1idiCkbHHzeEBk\WyuczDh[pRmeiB{IHjyd{BjgSCnbHXjeJJw[2inbXnseY1qdmW\|Y3XuZ4UtKEmFNUCgQUAxNjByMEig{txONg>?	NEnsOVk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOU[1OFQxQCd-MUm2OVQ1ODh:L3G+
RS4-11	MUDGeY5kfGmxbjDhd5NigQ>?		M{[ydlIhcHK\|	MnjCTY5pcWKrdHnvckBw\iCITGSzJGlVTCCvdYThcpQh[XW2b4Doc5NxcG:{eXzheIlwdiCrbjDoeY1idiCUU{StNVEh[2WubIOgZYZ1\XJiMjDodpMh[nliZXzlZ5Rzd2OqZX3pcJVucW6nc3PlcoNmKGG\|c3H5MEBKSzVyIE2gNE4xODFzIN88UU4>	NFf4VYc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOU[1OFQxQCd-MUm2OVQ1ODh:L3G+
AML	NXjl[GJjTnWwY4Tpc44h[XO\|YYm=			MnrvTY5pcWKrdHnvckBw\iCITGSzJIF2fG:yaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hSU2OIHPlcIx{KGm\|b3zheIVlKG[{b32gdoVt[XC\|ZXSgZYN2fGVibYnlcI9q\CCuZYXr[Y1q[SCyYYTp[Y51KGK7IGfld5Rmem5iYnzveJRqdmduIFnDOVAhRSByLkCwNkDPxE1w	M1n4WlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7NkW0OFA5Lz5zOU[1OFQxQDxxYU6=
RS4-11	MnfMSpVv[3Srb36gZZN{[Xl?		MlywNkBpenN?	NEG1T25KdmirYnn0bY9vKG:oIF\MWFMh[XW2b4Doc5NxcG:{eXzheIlwdiCrbjDoeY1idiCUU{StNVEh[2WubIOgZYZ1\XJiMjDodpMh[nliZXzlZ5Rzd2OqZX3pcJVucW6nc3PlcoNmKGG\|c3H5MEBKSzVyIE2gNE4xODR{IN88UU4>	NIfFN2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOU[1OFQxQCd-MUm2OVQ1ODh:L3G+
MV4-11	M4j0OGFvfGm2dX3vdkBie3OjeR?=	NITWbHEyOCCvZz;r[y=>	NYntXJV{PjBiZHH5dy=>	M3X3WWFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3WOE0yOSClZXzsd{B5\W6xZ4Lh[pRm\CCvb4Xz[UBud2SnbDDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIIT1cY9zKHKnZ4Lve5RpKGG2IHH0JFExKG2pL3vnMEBxdyB4MDDkZZl{KHCxc4SgeJJm[XSvZX70	NH;SRlQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOU[1OFQxQCd-MUm2OVQ1ODh:L3G+
MV4-11	NFXUWpFCdnSrdIXtc5Ih[XO\|YYm=	MXmxJI1oN2upL3ThfS=>	MoP4N\|Ah\GG7cx?=	M3rsfWFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3WOE0yOSClZXzsd{B5\W6xZ4Lh[pRm\CCvb4Xz[UBjd26nIH3hdpJwfyCnbnfyZYZ1dWWwdDDtc4RmdCCjc4Pld5Nm\CCjczDpcoNz\WG\|ZTDtc5V{\SCuaX\lJJNx[W5iYYSgNUBu\y:tZz;kZZktKHCxIH\vdkA{OCCmYYnzJI1m[XO3cnXkJI9vKGSjeTC3O{Bxd3O2IHTvd4U>	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTZ3NESwPEc,OTl4NUS0NFg9N2F-
MV4-11	Ml3JRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		MlzNO\|IhcHK\|	M2P3[mFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTW[0MVEyKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDj[YxtKHSrdHXyMYJtfWViY3XscEB3cWGkaXzpeJkh[XO\|YYmsJGlEPTBiPTCwMlAxODV4IN88UU4>	MlXGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl5NUSxPVkoRjF7N{W0NVk6RC:jPh?=
HEK293	MlvISpVv[3Srb36gZZN{[Xl?			MXfCbY5lcW6pIHHm[olvcXS7IITvJGZNXDNiY3H0ZYx6fGmlIHTvcYFqdiCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{KGK7IHPvcZBmfGm2aY\lJIJqdmSrbnegZZN{[XluIFvkJF0hOC5yMEG2JO69VS5?	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTd3NEG5PUc,OTl5NUSxPVk9N2F-
MV4-11	Mli4RY51cXS3bX;yJIF{e2G7	MWOxJI1oN2up	MUeyPEBl[Xm\|	NILGblZCdnSrdIXtc5Ih[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNWlQuOTFiY3XscJMhgGWwb3fyZYZ1\WRiaX6gZZRpgW2rYzDueYRmKG2xdYPlJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geJVud3JiZ4Lve5RpKGG2IEGgcYcwc2duIIDvJHFFKG[xcjCyPEBl[Xm\|IH3lZZN2emWmIHT1dolv\yCmb4PpcocheGW{aX;k	NIf6XGs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUe1OFE6QSd-MUm3OVQyQTl:L3G+
MV4-11	MVnBcpRqfHWvb4KgZZN{[Xl?	M4C3OVMhdWdxa3e=	MmjaNlgh\GG7cx?=	MXXBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPVkStNVEh[2WubIOgfIVvd2e{YX\0[YQhcW5iYYTofY1q[yCwdXTlJI1wfXOnIHHzd4V{e2WmIHHzJJR2dW:{IHfyc5d1cCC{ZXfy[ZN{cW:wIHH0JFMhdWdxa3esJJBwKFGGIH\vdkAzQCCmYYnzJI1m[XO3cnXkJIFnfGW{IHTvd4lv\yCyZYLpc4Q>	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTd3NEG5PUc,OTl5NUSxPVk9N2F-
MV4-11	NInnVoJCdnSrdIXtc5Ih[XO\|YYm=	NVPofXBYOTBibXevb4c>	NGGzU3MzQCCmYYnz	NYq4fGhiSW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gUXY1NTFzIHPlcIx{KHinbn;ndoFnfGWmIHnuJIF1cHmvaXOgcpVl\SCvb4Xz[UBie3Onc4Pl[EBieyC2dX3vdkBoem:5dHigdoVoemW\|c3nvckBifCBzMDDt[{9s\yxicH:gVWQh\m:{IEK4JIRigXNibXXhd5Vz\WRiYX\0[ZIh\G:\|aX7nJJBmemmxZB?=	NFntZZo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUe1OFE6QSd-MUm3OVQyQTl:L3G+
MV4-11	M{LxZWFvfGm2dX3vdkBie3OjeR?=	MXezJI1oN2up	M4TqSVI5KGSjeYO=	MnX2RY51cXS3bX;yJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTW[0MVEyKGOnbHzzJJhmdm:pcnHmeIVlKGmwIHH0bJlucWNiboXk[UBud3W\|ZTDhd5Nme3OnZDDhd{B{fXCycnXzd4lwdiCxZjD0eY1weiC4b3z1cYUh[XRiMzDt[{9s\yxicH:gVWQh\m:{IEK4JIRigXNibXXhd5Vz\WRiYX\0[ZIh\G:\|aX7nJJBmemmxZB?=	MkDnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl5NUSxPVkoRjF7N{W0NVk6RC:jPh?=
MV4-11	MXXBcpRqfHWvb4KgZZN{[Xl?	M4jNXFExKG2pL3vn	NGH0[FQzQCCmYYnz	MWrBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPVkStNVEh[2WubIOgfIVvd2e{YX\0[YQhcW5iYYTofY1q[yCwdXTlJI1wfXOnIHHzd4V{e2WmIHHzJJN2eHC{ZYPzbY9vKG:oIIT1cY9zKH[xbIXt[UBifCBzMDDt[{9s\yxicH:gVWQh\m:{IEK4JIRigXNibXXhd5Vz\WRiYX\0[ZIh\G:\|aX7nJJBmemmxZB?=	MlzZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl5NUSxPVkoRjF7N{W0NVk6RC:jPh?=
MV4-11	NFjqToxCdnSrdIXtc5Ih[XO\|YYm=	NWjKT2F4OTBibXevb4c>	MY[yPEBl[Xm\|	NYDjeVNLSW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gUXY1NTFzIHPlcIx{KHinbn;ndoFnfGWmIHnuJIF1cHmvaXOgcpVl\SCvb4Xz[UBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJR2dW:{IHfyc5d1cCCjdDCxNEBu\y:tZzygdI8hWURiZn;yJFI5KGSjeYOgcYVie3W{ZXSgZYZ1\XJiM{Kg[IF6eyCyb4P0[I9{\Q>?	MnTOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl5NUSxPVkoRjF7N{W0NVk6RC:jPh?=
MOLM13	MoLCRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?			MkSxRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPT1zNNVMh[2WubIOg[ZhxemW\|c3nu[{BHVFR\|LVnUSEBufXSjboSsJGdKPTBiPTCwMlAxPCEQvF2u	M4O2XlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{N{K2PVMyLz5{MkeyOlk{OTxxYU6=
MV411	NVPoSpZVT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MXW0PEBpenN?	M2nEdGdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJG1XPDFzIHPlcIx{KGGodHXyJFQ5KGi{czDifUBZXFRiYYPzZZktKEeLNUCgQUA{NjNzIN88UU4>	NVzHeZF2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWxNFgxPzlpPkK1NVA5ODd7PD;hQi=>
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HL60	MoiwS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		NEDKOWk1QCCqcoO=	M3PaWmdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJGhNPjBiY3XscJMh[W[2ZYKgOFghcHK\|IHL5JHhVXCCjc4PhfUwhT0l3MDC9JFgvODF2IN88UU4>	M4HsXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MUC4NFc6Lz5{NUGwPFA4QTxxYU6=
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MV4-11	M{DXfGZ2dmO2aX;uJIF{e2G7		M2W3c\|czKGi{cx?=	NFXSTo1KdmirYnn0bY9vKG:oIF\MWFMhUVSGIHjvcY97gWexdYOgcZV1[W62IHnuJIh2dWGwIF3WOE0yOSClZXzsd{Bie3Onc4Pl[EBieyClZXzsJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IEeyJIhzeyCkeTDNWHMh[XO\|YYmsJGdKPTBiPTCwMlAxOyEQvF2u	NYHIbpYzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFExOjNpPkK2NFgyODJ\|PD;hQi=>
MOLM-13	NG\mXnZHfW6ldHnvckBie3OjeR?=		NEjvbFg4OiCqcoO=	MV3Jcohq[mm2aX;uJI9nKE[OVEOgTXRFKGindHXyc5p6\2:3czDteZRidnRiaX6gbJVu[W5iTV;MUU0yOyClZXzsd{Bie3Onc4Pl[EBieyClZXzsJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IEeyJIhzeyCkeTDNWHMh[XO\|YYmsJGdKPTBiPTCwMlAxPCEQvF2u	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MUCyN{c,OjZyOEGwNlM9N2F-
32D	M2TtOmZ2dmO2aX;uJIF{e2G7		MmrKO\|IhcHK\|	NYjTSIVZUW6qaXLpeIlwdiCxZjDkdpVoKHKnc3nzeIFvfCCqdX3hckBHVFR\|IFnUSEBFQDN3WTDteZRidnRiZYjwdoV{e2WmIHnuJI1wfXOnIEOySEBk\WyuczDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFfJOVAhRSByLkCxOkDPxE1w	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MUCyN{c,OjZyOEGwNlM9N2F-
32D	NFHmVI1HfW6ldHnvckBie3OjeR?=		MVO3NkBpenN?	MVrJcohq[mm2aX;uJI9nKGS{dXegdoV{cXO2YX70JIh2dWGwIF\MWFMhUVSGIFS4N\|VXKG23dHHueEBmgHC{ZYPz[YQhcW5ibX;1d4UhOzKGIHPlcIx{KGG\|c3Xzd4VlKGG\|IHPlcIwh\3Kxd4ToJIlvcGmkaYTpc44h[W[2ZYKgO\|IhcHK\|IHL5JG1VWyCjc4PhfUwhT0l3MDC9JFAvODJ5IN88UU4>	NWHLfW9jRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFExOjNpPkK2NFgyODJ\|PD;hQi=>
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32D	NIj5R2pHfW6ldHnvckBie3OjeR?=		NFHpbos4OiCqcoO=	NUHF[GZIUW6qaXLpeIlwdiCxZjDkdpVoKHKnc3nzeIFvfCCqdX3hckBHVFR\|IFnUSEBFQDN3RjDteZRidnRiZYjwdoV{e2WmIHnuJI1wfXOnIEOySEBk\WyuczDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFfJOVAhRSByLkG1JO69VS5?	MknUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOEGwNlMoRjJ4MEixNFI{RC:jPh?=
32D	NIHlS\|dHfW6ldHnvckBie3OjeR?=		M2nke\|czKGi{cx?=	NF:ycZBKdmirYnn0bY9vKG:oIHTyeYchemW\|aYP0ZY51KGi3bXHuJGZNXDNiSWTEJGY3QTGOIH31eIFvfCCneIDy[ZN{\WRiaX6gcY92e2ViM{LEJINmdGy\|IHHzd4V{e2WmIHHzJINmdGxiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPzJiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDBwMkKg{txONg>?	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MUCyN{c,OjZyOEGwNlM9N2F-
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MV4-11	NUPle5NTTnWwY4Tpc44h[XO\|YYm=	Mlj1NUBvVQ>?	MlTRNUBpeg>?	MUjJcohq[mm2aX;uJI9nKE[OVEOgTXRFKG23dHHueEBifXSxcHjvd5Bpd3K7bHH0bY9vKGG2IGm1PFkwPTlzIHnuJIh2dWGwIF3WOE0yOSClZXzsd{BifCBzIH7NJIFnfGW{IEGgbJIh[nliaX3teY5w[myxdDDhcoFtgXOrcx?=	NETXT4w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[3NlA1QSd-Mkm2O\|IxPDl:L3G+
MV4-11	NXLoV5NzTnWwY4Tpc44h[XO\|YYm=	MWOxJI5O	NILEencyKGi{	NFSxUJhKdmirYnn0bY9vKG:oIF\MWFMhUVSGIH31eIFvfCCjdYTvdIhwe3Cqb4L5cIF1cW:wIHH0JHk5PDJiaX6gbJVu[W5iTW[0MVEyKGOnbHzzJIF1KDFibl2gZYZ1\XJiMTDodkBjgSCrbX31co9jdG:2IHHuZYx6e2m\|	M17Nb\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkeyNFQ6Lz5{OU[3NlA1QTxxYU6=
MV4-11	M1PRUGZ2dmO2aX;uJIF{e2G7	M1juS\|AvODFidH:gNVAxKG6P	NGnleHQyKGi{	M2LubGlvcGmkaYTpc44hd2ZiRlzUN{BKXERibYX0ZY51KGmwIHj1cYFvKE2YND2xNUBk\WyuczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiCVVFHUOUBxcG:\|cHjvdplt[XSrb36gZZQhYTZ7NDDheEAxNjBzIITvJFExOCCwTTDh[pRmeiBzIHjyJIJ6KGmvbYXuc4Jtd3RiYX7hcJl{cXN?	NITpelM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[3NlA1QSd-Mkm2O\|IxPDl:L3G+
MV4-11	M3W3NWZ2dmO2aX;uJIF{e2G7	MY[wMlAyKHSxIEGwNEBvVQ>?	NH30OZgyKGi{	NYr6fXl{UW6qaXLpeIlwdiCxZjDGUHQ{KEmWRDDteZRidnRiaX6gbJVu[W5iTW[0MVEyKGOnbHzzJIF{e2W\|c3XkJIF{KGSnY4LlZZNmKGmwIFXST\|EwOiCyaH;zdIhwenmuYYTpc44h[XRiVEKwNk9[OjB2IHH0JFAvODFidH:gNVAxKG6PIHHmeIVzKDFiaIKgZpkhcW2vdX7vZoxwfCCjbnHsfZNqew>?	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ5MkC0PUc,Ojl4N{KwOFk9N2F-
MV4-11	NHvTS3RHfW6ldHnvckBie3OjeR?=	M4nweVExKG2pL3vn	MYCyOEBpenN?	M{Xld2lvKH[rdn:gbY5pcWKrdHnvckBw\iCITGSzJGlVTCCvdYThcpQhcW5iaIXtZY4hVVZ2LUGxJINmdGy\|IIjlco9oemGodHXkJIlvKGG2aIntbYMhdnVxboWgcY92e2ViYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4hW1SDVEWgdIhwe3Cqb4L5cIF1cW:wIHH0JHk3QTRiYYSgNVAhdWdxa3esJIlxKGGodHXyJFI1KGi{czDifUBqdW23bn;icI91KG2ndHjv[EBz\WyjdHn2[UB1dyClb370do9t	NXPqdphVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2O\|IxPDlpPkK5OlczODR7PD;hQi=>
MV4-11	Ml3OSpVv[3Srb36gZZN{[Xl?	MXmwMlEhfU1?	MkHZOEBpenN?	MV7Jcohq[mm2aX;uJI9nKE[OVEOgbY4hcHWvYX6gUXY1NTFzIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBCU1RicHjvd5Bpd3K7bHH0bY9vKGG2IGPldlQ4OyC{ZYPp[JVmKGG2IECuNUB2VSCjZoTldkA1KGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN?	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTh7NEm0OEc,Ojl6OUS5OFQ9N2F-
MV4-11	NH7UW3RHfW6ldHnvckBie3OjeR?=	NYrRUWRkOC5zIIXN	NFrGblY1KGi{cx?=	M4L5XmlvcGmkaYTpc44hd2ZiRlzUN{BqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKFOWQWS1JJBpd3OyaH;yfYxifGmxbjDheEBVgXJ4OUSgdoV{cWS3ZTDheEAxNjFidV2gZYZ1\XJiNDDodpMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz	NH3i[GY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUi5OFk1PCd-Mkm4PVQ6PDR:L3G+
MV4-11	MVPGeY5kfGmxbjDhd5NigQ>?	NX7jSVJXOC5zIIXN	NIX4cY81KGi{cx?=	M1:wcmlvcGmkaYTpc44hd2ZiRlzUN{BqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKEWUS{GvNkBxcG:\|cHjvdplt[XSrb36gZZQhXGi{MkCyM3R6ejJyNDDy[ZNq\HWnczDheEAxNjFidV2gZYZ1\XJiNDDodpMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz	M1i1[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OEm0PVQ1Lz5{OUi5OFk1PDxxYU6=
MV4-11	NIjxNG9HfW6ldHnvckBie3OjeR?=	Mn7tNE4yKHWP	NU\R[mZ1PCCqcoO=	NEfHO\|hKdmirYnn0bY9vKG:oIF\MWFMheGixc4Doc5J6dGG2aX;uJIF1KFS7ckW4PU82QTFicnXzbYR2\XNiaX6gbJVu[W5iTW[0MVEyKGOnbHzzJIF1KDBwMTD1UUBi\nSncjC0JIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	NFTMbFA9[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	p-STAT5 / STAT5 / β-catenin / p-AKT / AKT / p-ERK / ERK / p-S6 / S6 ; phospho-FLT3 / FLT3	28625976 22875611
Immunofluorescence	WGA / FLT3	28895560
Growth inhibition assay	Cell viability	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 (from reference)

Kinase Assay:^[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
Cell Research:^[1]	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]	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

Molecular Weight	560.67
Formula	C₂₉H₃₂N₆O₄S
CAS No.	950769-58-1
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC(C)(C)C1=CC(=NO1)NC(=O)NC2=CC=C(C=C2)C3=CN4C5=C(C=C(C=C5)OCCN6CCOCC6)SC4=N3

Download Quizartinib (AC220) SDF

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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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.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
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Molarity Calculator

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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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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

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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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