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I-BET151 (GSK1210151A)

Name: I-BET151 (GSK1210151A)
Brand: Selleck Chemicals
SKU: S2780
Rating: 5 (39 reviews)

Catalog No.S2780

For research use only.

I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively.

I-BET151 (GSK1210151A) Chemical Structure

CAS No. 1300031-49-5

Selleck's I-BET151 (GSK1210151A) has been cited by 39 publications

Purity & Quality Control

Choose Selective Epigenetic Reader Domain Inhibitors

Related Compound Libraries

Biological Activity

Description

I-BET151 (GSK1210151A) is a novel selective BET inhibitor for BRD2, BRD3 and BRD4 with IC50 of 0.5 μM, 0.25 μM, and 0.79 μM in cell-free assays, respectively.

Features

Optimized to retain excellent BET target potency and selectivity while enhancing the in vivo pharmacokinetics and terminal half-life to enable prolonged in vivo studies.

Targets

BRD3 ^[1] (Cell-free assay)	BRD2 ^[1] (Cell-free assay)	BRD4 ^[1] (Cell-free assay)
0.25 μM	0.5 μM	0.79 μM

In vitro

I-BET151 exhibits potent selectivity over an extensive range of diverse protein types such as COX-2, P450, Aurora B, GSK3β, PI3K-γ, GPCR, ion channels, and transporters. Similar to I-BET762 (GSK525762A), I-BET151 displays potent binding affinity to BRD2, BRD3 and BRD4 with K_D of 0.02-0.1 μM, and significantly inhibits lipopolysaccharide-stimulated IL-6 cytokine production in human peripheral blood mononuclear cells (PBMC) and whole blood (WB) as well as rat WB with IC50 of 0.16 μM, 1.26 μM, and 1.26 μM, respectively. I-BET151 (0.5 or 5 μM) inhibits the binding of BETs (BRD2, BRD3, BRD4, and BRD9) but not the binding of 23 other bromodomain proteins in HL60 nuclear extract to acetylated histone peptides. I-BET151 has potent efficacy against cell lines harboring different MLL-fusions such as MV4;11, RS4;11, MOLM13, and NOMO1 cells with IC50 of 15-192 nM. Consistently, I-BET151 completely ablates the colony-forming potential of MLL-fusion-driven leukaemias (MOLM13) but not leukaemias driven by tyrosine kinase activation (K562). I-BET151 also displays potent efficacy in both liquid culture and clonogenic assays using primary murine progenitors transformed with either MLL-ENL or MLL-AF9. I-BET151 treatment significantly induces apoptosis and prominent G0/G1 arrest in MLL-fusion cell lines driven by distinct MLL fusions (MOLM13 and MV4;11 containing MLL-AF9 and MLL-AF4, respectively) but not the K562 cells, probably due to the inhibition of transcription of BCL2, C-MYC and CDK6 by blocking the recruitment of BRD3/4, PAFc and SEC components into transcriptional start site (TSS). ^[1]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

MV4;11	Mo\LZ5l1d3SxeHnjbZR6KGG\|c3H5	NWmyeGh3hjFyMDFOwG0>		Mlv3SG1UVw>?	NEXpZm1KSzVyPUK2JI5O	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
RS4;11	M2\XZ4N6fG:2b4jpZ4l1gSCjc4PhfS=>	Ml[5glExOCEQvF2=		MmPUSG1UVw>?	MVnJR\|UxRTF7MjDuUS=>	MnrXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
MOLM13	NXnaVm9H[3m2b4TvfIlkcXS7IHHzd4F6	NGHyZXh,OTByIN88US=>		MWTEUXNQ	NEPtWmRKSzVyPUGyNEBvVQ>?	M1;3VVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
NOMO1	NUfYO2lx[3m2b4TvfIlkcXS7IHHzd4F6	M1\JNp4yODBizszN		M{TLZ2ROW09?	MmDyTWM2OD1zNTDuUS=>	NWLDfYltRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
HEL	NFP6NJlkgXSxdH;4bYNqfHliYYPzZZk>	MkTzglExOCEQvF2=		NUXo[I1sTE2VTx?=	NXPqVGM6UUN3ME2xJO69VQ>?	M4TSb\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
K562	M1m5V4N6fG:2b4jpZ4l1gSCjc4PhfS=>	MWn+NVAxKM7:TR?=		M{TrUWROW09?	Mnj1TWM2OD5zMECg{txO	NYDQfWt5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
MEG01	Mof2Z5l1d3SxeHnjbZR6KGG\|c3H5	MVf+NVAxKM7:TR?=		MnG1SG1UVw>?	MYnJR\|UxRTJ3IN88US=>	Moq3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
HL60	MYfjfZRwfG:6aXPpeJkh[XO\|YYm=	MljFglExOCEQvF2=		NUL1OHZqTE2VTx?=	MlXwTWM2OD16OUCgcm0>	NFfiOIU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
MV4;11	MWDBdI9xfG:\|aYOgZZN{[Xl?	NHPGXph,OTByIN88US=>		NH[2dZJFVVOR	MXTpcoR2[2W\|IHHwc5B1d3Orcx?=	NHrLbo49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
MOLM13	M{nBfGFxd3C2b4Ppd{Bie3OjeR?=	MW\+NVAxKM7:TR?=		MnL1SG1UVw>?	MUjpcoR2[2W\|IHHwc5B1d3Orcx?=	Ml\yQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
MV4;11	NF3uPZpHfW6ldHnvckBie3OjeR?=			NFzPNpdFVVOR	MlPn[IVkemWjc3XzJJRp\SC{ZXPyeYl1dWWwdDDv[kBDWkR\|L{SgZY5lKGmvcHHpdoVlKHKnY4L1bZRu\W62IH;mJGNFUzliYX7kJHBCTjFidH:geIhmKHS{YX7zZ5JqeHSrb37hcEB{fGG{dDDzbZRm	NUDLOWZbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
PBMC	MlnuSpVv[3Srb36gZZN{[Xl?			MnvNSG1UVw>?	MlvybY5pcWKrdIOgTWwuPiC5aYToJJBKSzVyIH;mJFYvPw>?	NHL5RWw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkSzO\|EyPSd-MkK0N\|cyOTV:L3G+
A2	MXPGeY5kfGmxbjDhd5NigQ>?	M2HaPZ4yOCEQvF2=		NWL6T2piTE2VTx?=	NHq4[5dz\WGldHn2ZZRmeyCuYYTlcpQhUEmYLUG=	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ3NUKxPEc,OjN{NUWyNVg9N2F-
A72	MX3GeY5kfGmxbjDhd5NigQ>?	M2\YRp4yOCEQvF2=		M{TJfmROW09?	NEnndHpz\WGldHn2ZZRmeyCuYYTlcpQhUEmYLUG=	NUni[YZYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyOVUzOThpPkKzNlU2OjF6PD;hQi=>
BC1	MXTHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NVLUOIhEhjFizszN		NXLuUJZyTE2VTx?=	MYXJR\|UxRTJ{MDDuUS=>	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC3	NYf3dG9xT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MVX+NUDPxE1?		NXjvO3BKTE2VTx?=	NHjkOVJKSzVyPUS2NEBvVQ>?	M{[zbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BCBL1	MmXpS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MXj+NUDPxE1?		NXr4dIxLTE2VTx?=	NXPrT\|RJUUN3ME2zN\|Ahdk1?	M3\3R\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BJAB	NVnDXnU3T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MYH+NUDPxE1?		MoHYSG1UVw>?	MVLJR\|UxRTl5MDDuUS=>	NIO5Xnc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
Namalwa	NGr3O\|ZIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NESzN4h,OSEQvF2=		NEH3THBFVVOR	Ml;yTWM2OD17N{Cgcm0>	M1PlOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
Jurkat	M3HQZmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MXv+NUDPxE1?		M{PtU2ROW09?	NF:5[Y5KSzVyPUGyNlAhdk1?	NXPCcJRlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
MM1S	M1rjWWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MoDnglEh\|ryP		M4rTS2ROW09?	MlvGTWM2OD15NkCgcm0>	NEjBeHE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
U266	MUHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NX3YZoh5hjFizszN		M4\hW2ROW09?	NWD3Z4xDUUN3ME25OVAhdk1?	Mm\IQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
UM-PEL-1	MUHHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NYn4TI5ohjFizszN		Ml25SG1UVw>?	MoW5TWM2OD1{MUCgcm0>	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
UM-PEL-3	MnTFS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MVP+NUDPxE1?		M{fLcmROW09?	M{PUNmlEPTB;MUiwJI5O	NEi0[YY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BC1	MmjJSpVv[3Srb36gZZN{[Xl?	Mo\kOVAxKG6P		M2q4ZmROW09?	Mk\FbY5lfWOnczDj[YxtNWO7Y3zlJIFzemW\|dB?=	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC3	Ml2xSpVv[3Srb36gZZN{[Xl?	MUW1NFAhdk1?		MkTrSG1UVw>?	NGCyZ5NqdmS3Y3XzJINmdGxvY4njcIUh[XK{ZYP0	MoThQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
BC1	M2jibmZ2dmO2aX;uJIF{e2G7	NFmzWJU5ODBibl2=		M3H0XWROW09?	NXf5TnFPemWmdXPld{BkNU27YzDwdo91\WmwIHzleoVtew>?	M13sVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BC3	MYnGeY5kfGmxbjDhd5NigQ>?	MkiwPFAxKG6P		MXrEUXNQ	M3K1OpJm\HWlZYOgZ{1OgWNicILveIVqdiCuZY\lcJM>	MkDsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
H929	M{mzTmZ2dmO2aX;uJIF{e2G7	NVPiZoRYhjFizszN		MUHEUXNQ	M3frVolv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S=	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS12PE	M1zlO2Z2dmO2aX;uJIF{e2G7	NWfxboMyhjFizszN		M1rHOmROW09?	NYH4VIVncW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=>	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS12BM	Mn2xSpVv[3Srb36gZZN{[Xl?	M1LBSJ4yKM7:TR?=		MX\EUXNQ	MYjpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	NUTvRZdKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS18	M3zCVWZ2dmO2aX;uJIF{e2G7	NFjibFF,OSEQvF2=		MmLySG1UVw>?	MnjFbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	Mmq2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
KMS11	MlnvSpVv[3Srb36gZZN{[Xl?	NXThN5R5hjFizszN		M4qyOWROW09?	NIPDXYRqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	M4TtbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
RPMI8226	M3HDV2Z2dmO2aX;uJIF{e2G7	MUn+NUDPxE1?		NYrveG5vTE2VTx?=	MlfTbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	M17kclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
H929	MlfqRZBweHSxc3nzJIF{e2G7	MkDzglEh\|ryP		M3PtXWROW09?	NF7GZ5BqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	NVnidZpORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS12PE	M3L4S2Fxd3C2b4Ppd{Bie3OjeR?=	NIrsXVJ,OSEQvF2=		NX\5dZlJTE2VTx?=	NHjlPJJqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	MojWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
KMS12BM	M3;KbWFxd3C2b4Ppd{Bie3OjeR?=	MUn+NUDPxE1?		M2DicWROW09?	M2nzeIlv\HWlZYOgZ4VtdCCjcH;weI9{cXN?	M2TmUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS18	MYfBdI9xfG:\|aYOgZZN{[Xl?	MWr+NUDPxE1?		NFXBc4JFVVOR	MkS2bY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?	MkfrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
KMS11	NEfxWmZCeG:ydH;zbZMh[XO\|YYm=	MWT+NUDPxE1?		M2PlfGROW09?	NWj4[4Q1cW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	M37GWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
RPMI8226	MkC5RZBweHSxc3nzJIF{e2G7	NH\ZV2x,OSEQvF2=		MX;EUXNQ	NUfCNIREcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	NIfQS2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
U87MG	M4q0XWZ2dmO2aX;uJIF{e2G7	NXPMO4JThjFyIN88US=>		MUjEUXNQ	MV3y[YR2[2W\|IGW4O21IKGOnbHz1cIFzKEGWUDD3bZRpKEmFNUCgc4YhOS5yNTFOwG0>	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7NkO4NUc,OjR2OU[zPFE9N2F-
A172	MXrGeY5kfGmxbjDhd5NigQ>?	NY\iPGxKhjFyIN88US=>		MoG3SG1UVw>?	NWXGWphNemWmdXPld{Bk\WyudXzhdkBCXFBid3n0bEBKSzVyIH;mJFEvOjhizszN	NF3rWIg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OlM5OSd-MkS0PVY{QDF:L3G+
SW1783	M1;a[GZ2dmO2aX;uJIF{e2G7	MWf+NVAh\|ryP		NXHuO3BnTE2VTx?=	MX;y[YR2[2W\|IHPlcIx2dGG{IFHUVEB4cXSqIFnDOVAhd2ZiMj62PEDPxE1?	MnfjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OU[zPFEoRjJ2NEm2N\|gyRC:jPh?=
U87MG	NE\tU3RHfW6ldHnvckBie3OjeR?=	NVH4fVNEhjFyIN88US=>		NFjTSItFVVOR	M3rnZ4lv[3KnYYPld{Bxem:yb4L0bY9vKG:oIHPlcIx{KGmwIITo[UBIOS:VIITyZY5{cXSrb36=	NHzwd4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OlM5OSd-MkS0PVY{QDF:L3G+
RAW267.4	NUXtTYhUTnWwY4Tpc44h[XO\|YYm=	NGXSXpgyKM7:TR?=		MlWzSG1UVw>?	MYTy[YR2[2W\|IFnMMVYheHKxZIXjeIlwdiCrbnT1Z4VlKGK7IFzQVy=>	NHzVOHg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEi1PVAxQCd-MkS4OVkxODh:L3G+
RAW267.4	NIe4[ldHfW6ldHnvckBie3OjeR?=	MYWxJO69VQ>?		MYPEUXNQ	M{ewdZJm\HWlZYOgeIhmKGG\|c3;jbYF1cW:wIHLleJdm\W5iQmLEOEBidmRiYXPleJlt[XSnZDDwOlU>	MoOxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6NUmwNFgoRjJ2OEW5NFA5RC:jPh?=
Me007	NHm5V2VIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NHT1UIJ,OTByIN88US=>		NH\repVFVVOR	MojibY5pcWKrdIOgeIhmKGe{b4f0bC=>	NFfSVoQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
SK-Mel-28	MlX6S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M1XseZ4yODBizszN		MVLEUXNQ	NXrqOW5NcW6qaXLpeJMhfGinIHfyc5d1cA>?	M1rDe\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	MnfnS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MmLxglExOCEQvF2=		NX;VcZVzTE2VTx?=	Mn7FbY5pcWKrdIOgeIhmKGe{b4f0bC=>	M1jFXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-JD	MWnHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	MmXMglExOCEQvF2=		M1LnOGROW09?	M2rFfolvcGmkaYTzJJRp\SCpcn;3eIg>	MkH5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-RM	NInUcWdIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	M{DsfJ4yODBizszN		NGjjS\|hFVVOR	MX\pcohq[mm2czD0bIUh\3Kxd4To	MkHtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Me007	NV7HfWtPSXCxcITvd4l{KGG\|c3H5	NHP4[\|B,OTByIN88US=>		NXP5TW9WTE2VTx?=	MYXpcoR2[2W\|IHHwc5B1d3Orcx?=	NXv4OFM2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
SK-Mel-28	NF;B[WtCeG:ydH;zbZMh[XO\|YYm=	NUHMZo11hjFyMDFOwG0>		M{HWOWROW09?	MnTKbY5lfWOnczDhdI9xfG:\|aYO=	NFy1[3U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RMU	MUjBdI9xfG:\|aYOgZZN{[Xl?	MYn+NVAxKM7:TR?=		NYT6XI92TE2VTx?=	MWHpcoR2[2W\|IHHwc5B1d3Orcx?=	M{DYNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-JD	NIPYR25CeG:ydH;zbZMh[XO\|YYm=	M37tcZ4yODBizszN		NH\Nc4xFVVOR	MWrpcoR2[2W\|IHHwc5B1d3Orcx?=	NX\nTZhQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RM	MkfpRZBweHSxc3nzJIF{e2G7	MUH+NVAxKM7:TR?=		NGjNdIlFVVOR	M2LDO4lv\HWlZYOgZZBweHSxc3nz	NVLwdWVbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Me007	NHjDSIdHfW6ldHnvckBie3OjeR?=	MWSxNEDPxE1?		NYn2fXJWTE2VTx?=	NFLuO4RqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIJ6KHWycnXneYxifGmxbjDv[kBxOjF?	NYXZfXdWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
SK-Mel-28	MnG3SpVv[3Srb36gZZN{[Xl?	NFqyXXUyOCEQvF2=		MXnEUXNQ	M2fNNolv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	M1zHeFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	MmXVSpVv[3Srb36gZZN{[Xl?	M2rJWFExKM7:TR?=		NUjGRXh[TE2VTx?=	MoHHbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dDDifUB2eHKnZ4XsZZRqd25ib3[gdFIy	MoPnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-JD	MYXGeY5kfGmxbjDhd5NigQ>?	MV2xNEDPxE1?		M{LqUWROW09?	M1TCb4lv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RM	MX\GeY5kfGmxbjDhd5NigQ>?	NHrubZYyOCEQvF2=		NH2y[WdFVVOR	MXnpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2IHL5JJVxemWpdXzheIlwdiCxZjDwNlE>	NXnW[Gg5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Me007	NHP3TWxHfW6ldHnvckBie3OjeR?=	NYXrTlN3OTBizszN		M{Xhc2ROW09?	NIHEdJV2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	NWXPNGRZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
SK-Mel-28	M37XdmZ2dmO2aX;uJIF{e2G7	NFvFNpUyOCEQvF2=		MXPEUXNQ	NHrXWmd2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	NWS0[HRWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RMU	Mm\RSpVv[3Srb36gZZN{[Xl?	MoTCNVAh\|ryP		NFHVfJVFVVOR	M3PYZZVxemWpdXzheIV{KHC{b3Hwc5B1d3SrYzDhcoQh[2WubDDjfYNt\SCjcoLld5Qh\2WwZYO=	M{fndlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-JD	MkDRSpVv[3Srb36gZZN{[Xl?	MlrmNVAh\|ryP		NIiydVJFVVOR	M1vCbpVxemWpdXzheIV{KHC{b3Hwc5B1d3SrYzDhcoQh[2WubDDjfYNt\SCjcoLld5Qh\2WwZYO=	NE\ySIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RM	NEfWTnlHfW6ldHnvckBie3OjeR?=	MkfXNVAh\|ryP		M{\aO2ROW09?	NU\5ZnFOfXC{ZXf1cIF1\XNicILvZZBweHSxdHnjJIFv\CClZXzsJIN6[2ynIHHydoV{fCCpZX7ldy=>	NYDOT3R5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
HepG2	NXrzbpFxTnWwY4Tpc44h[XO\|YYm=		MUSxPEBpenN?		NELsZ3NWeHKnZ4XsZZRqd25ib3[gRZBwSTFiZYjwdoV{e2mxbjDpckBpfW2jbjDI[ZBIOiClZXzsd{Bie3Onc4Pl[EBieyClb37j[Y51emG2aX;uJJJmeXWrcnXkJJRwKGmwY4LlZZNmKDdyJTDv[kBtfWOrZnXyZZNmKGGldHn2bZR6KGGodHXyJFE5KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFXDNVcxKD1iMD6wPUDPxE1w	NXHtR5Y{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzPFY2OjlpPkKyN\|g3PTJ7PD;hQi=>
Raji	MV7GeY5kfGmxbjDhd5NigQ>?		MX20JIhzew>?		Mn\WTY5pcWKrdHnvckBw\iCEUlS0JIlvKGi3bXHuJHJicmliY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIH;mJG1[SyCneIDy[ZN{cW:wIHHmeIVzKDRiaILzMEBKSzVyIE2gNE4yOyEQvF2u	NFvQN\|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFc2QCd-MkS5NFA4PTh:L3G+
MV4-11	M2jucmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MUW3NkBpenN?		NEXpW4JIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBOXjRvMUGgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NEA:KDBwMUG5JO69VS5?	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTV3OUSyPEc,OjV3NUm0Nlg9N2F-
MM1S	MY\Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		Ml\DO\|IhcHK\|		MlSyS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gUW0yWyClZXzsd{Bi\nSncjC3NkBpenNiYomgV3JDKGG\|c3H5MEBKSzVyIE2gNE4zQTlizszNMi=>	NWXFeog6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1OVk1OjhpPkK1OVU6PDJ6PD;hQi=>
HT-29	MkjkS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		MnLQO\|IhcHK\|		NUTGOFVKT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hUFRvMkmgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NEA:KDBwOUS1JO69VS5?	NGXoOZU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUW1PVQzQCd-MkW1OVk1Ojh:L3G+
Rosetta2 DE3	NVjUOmhvTnWwY4Tpc44h[XO\|YYm=		NXHGUWNzOzBibXnudy=>		NUPzXYd7TGm\|cHzhZ4Vu\W62IH;mJGZCVS2uYXLlcIVlKFqEQUK0PEBnem:vIFLSSFQhSkRzIDi0OEB1dyBzNkigZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvODNzNzFOwG0v	NIHjWJU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
MV4-11	MYXDfZRwfG:6aXPpeJkh[XO\|YYm=		Mln4OEBl[Xm\|		MXPDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNWlQuOTFiY3XscJMhcGG{Yn;ybY5oKE2OTEGg[pV{cW:wIHflcoUh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPCCmYYnzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[XO\|YYmsJGlEPTBiPTCwMlE3OiEQvF2u	NIS2PIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	Mnj1SpVv[3Srb36gZZN{[Xl?		MV6zNEBucW6\|		MW\EbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGNDDCSFIhMDN\|MzD0c{A1PjBiYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygTWM2OCB;IECuNlI3KM7:TT6=	Mk[3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
MOLM13	M{npWWN6fG:2b4jpZ4l1gSCjc4PhfS=>		NG\jb3k1KGSjeYO=		NFXReFREgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOV0yPMUOgZ4VtdHNiaHHyZo9zcW6pIF3MUFEh\nW\|aX;uJIdmdmViYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiNDDkZZl{KGK7IFPlcIxVcXSncj3HcI8hdHWvaX7ld4NmdnRiYYPzZZktKEmFNUCgQUAxNjJ{ODFOwG0v	M2XjR\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MkXhSpVv[3Srb36gZZN{[Xl?		MYWzNEBucW6\|		MoruTY5pcWKrdHnvckBw\iCIQV2tcIFj\WynZDDaRmEzPDhiYnnu[Ilv\yC2bzDy[YNwdWKrbnHueEBpfW2jbjDOMZRmem2rbnHsJGhqezZvdHHn[4VlKEKURESgZpJwdW:mb33hbY4hOSBqNESgeI8hOTZ6IILld4llfWW\|KTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkhTmyxdYLld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygTWM2OCB;IECuNFMyPyEQvF2u	NWXaWJA1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
MV4-11	M3TNRWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NH;Kd\|E1KGSjeYO=		MWrHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDNWlQuOTFiY3XscJMh[W[2ZYKgOEBl[Xm\|IHL5JHdUXC16IHHzd4F6NCCLQ{WwJF0hOC5zNkKg{txONg>?	M{LyVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NE[zOFg4Lz5{OES2N\|Q5PzxxYU6=
Rosetta2 DE3	NFT0UWVHfW6ldHnvckBie3OjeR?=		MX:zNEBucW6\|		NFnsO5lKdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiB{IDizN\|MhfG9iNE[wJJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvOjJ4IN88UU4>	M{fNZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NE[zOFg4Lz5{OES2N\|Q5PzxxYU6=
MOLM13	MnPzS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		M2HSNlQh\GG7cx?=		NVjXZY9bT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVU:OTUGzJINmdGy\|IHHmeIVzKDRiZHH5d{BjgSCZU2StPEBie3OjeTygTWM2OCB;IECuNlI5KM7:TT6=	MmLKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2NkO0PFcoRjJ6NE[zOFg4RC:jPh?=
Rosetta2 DE3	NUfqTHNuTnWwY4Tpc44h[XO\|YYm=				NIjtfGtDcW6maX7nJIFn\mmwaYT5JJRwKGKrb4Tpcplt[XSnZDDCVmQ{KEKGMTCoNlQhfG9iMUS0JIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDifUBjcW9vbHH5[ZIhcW62ZYLm[ZJwdWW2comgcYV1cG:mLDDL[EA:KDBwMEK5PEDPxE1w	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	M4nSNGZ2dmO2aX;uJIF{e2G7				NHO0UphDcW6maX7nJIFn\mmwaYT5JJRwKGKrb4Tpcplt[XSnZDDCVmQ{KEKGMjCoN\|A3KHSxIESxO{BidWmwbzDhZ4llKHKnc3nkeYV{MSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDSc5NmfHSjMjDESVMh[2WubIOgZpkh[mmxLXzhfYVzKGmwdHXy[oVzd22ndIL5JI1mfGixZDygT4QhRSByLkC0NFUh\|ryPLh?=	Ml\KQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	NHXZeZJHfW6ldHnvckBie3OjeR?=				NXv3bXVxSmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgRnJFPCCEREGgLFQ1KHSxIEG2PEBidWmwbzDhZ4llKHKnc3nkeYV{MSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDSc5NmfHSjMjDESVMh[2WubIOgZpkh[mmxLXzhfYVzKGmwdHXy[oVzd22ndIL5JI1mfGixZDygT4QhRSByLkC1Nlgh\|ryPLh?=	NHvhUo09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	MVTGeY5kfGmxbjDhd5NigQ>?				MnW4Rolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQmLENkBDTDFiKEeyJJRwKDJyNTDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYomgZolwNWyjeXXyJIlvfGW{ZnXyc41mfHK7IH3leIhw\CxiS3SgQUAxNjB3NEig{txONg>?	NUHVcI1SRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	MUnGeY5kfGmxbjDhd5NigQ>?				NEG2dHZDcW6maX7nJIFn\mmwaYT5JJRwKGKrb4Tpcplt[XSnZDDCVmQzKEKGMjCoN\|Q6KHSxIES2NEBidWmwbzDhZ4llKHKnc3nkeYV{MSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDSc5NmfHSjMjDESVMh[2WubIOgZpkh[mmxLXzhfYVzKGmwdHXy[oVzd22ndIL5JI1mfGixZDygT4QhRSByLkC3NFMh\|ryPLh?=	MluxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	MWnGeY5kfGmxbjDhd5NigQ>?				NWfp[G1sSmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgRnJFPCCEREKgLFM{OyC2bzC0OlAh[W2rbn:gZYNq\CC{ZYPp[JVmeyliKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gVo9{\XS2YUKgSGU{KGOnbHzzJIJ6KGKrbz3sZZlmeiCrboTldoZmem:vZYTyfUBu\XSqb3SsJGtlKD1iMD6yNVUh\|ryPLh?=	NUjlc4NYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	MmHySpVv[3Srb36gZZN{[Xl?				NUDacpI2SmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgR3JGSkKSIDixNFQ{KHSxIEGxOVkh[W2rbn:gZYNq\CC{ZYPp[JVmeyliKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gVo9{\XS2YUKgSGU{KGOnbHzzJIJ6KGKrbz3sZZlmeiCrboTldoZmem:vZYTyfUBu\XSqb3SsJGtlKD1iMz6wPFQh\|ryPLh?=	M3j3UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	M3f1XmZ2dmO2aX;uJIF{e2G7		M2G1PFMxKG2rboO=		M2jjZWRqe3CuYXPlcYVvfCCxZjDGRW0udGGkZXzl[EBbSkF{NEig[pJwdSCEUlSzJGJFOSBqMkSgeI8hOTR2IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGtqKD1iMD6wNFczKM7:TT6=	Mo\BQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	MVHGeY5kfGmxbjDhd5NigQ>?		NWf1UmhpOzBibXnudy=>		MnjpSIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKURESgRmQyKCh2NDD0c{AyPjhiYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkCwPUDPxE1w	NID6RWU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	MYTGeY5kfGmxbjDhd5NigQ>?		NFjYTos{OCCvaX7z		MnnNSIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKUREKgRmQyKCh5MjD0c{AzODViYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkCwPUDPxE1w	NFzNbWI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	NGi2U3hHfW6ldHnvckBie3OjeR?=		Mn;yN\|AhdWmwcx?=		Mn71SIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKUREOgRmQzKCh\|ME[geI8hPDF5IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGtqKD1iMD6wNlI{KM7:TT6=	M{e4bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NXrRZXp[TnWwY4Tpc44h[XO\|YYm=		MoLXN\|AhdWmwcx?=		NVz0eGpETGm\|cHzhZ4Vu\W62IH;mJGZCVS2uYXLlcIVlKFqEQUK0PEBnem:vIFLSSFIhSkR{IDizOFkhfG9iNE[wJIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDh[pRmeiB\|MDDtbY5{KGK7IH\seY9z\XOlZX7j[UBxd2yjcnn6ZZRqd25iYYPzZZktKEurIE2gNE4xPDl4IN88UU4>	NWfvco17RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	NYTQT3ZnTnWwY4Tpc44h[XO\|YYm=		NY\BT5ZNOzBibXnudy=>		MnToSIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKURESgRmQzKCh\|M{OgeI8hPDZyIHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGtqKD1iMD6wO\|Q5KM7:TT6=	MnnIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	M3;tO2Z2dmO2aX;uJIF{e2G7		M1zzVFMxKG2rboO=		M3O4[WlvcGmkaYTpc44hd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IHLpcoRqdmdidH:gdoVkd22kaX7hcpQhcHWvYX6gUk11\XKvaX7hcEBJcXN4LYTh[4dm\CCEUlS0JIJzd22xZH;tZYlvKDFiKES0JJRwKDF4ODDy[ZNq\HWnczmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KE[ub4Xy[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGtqKD1iMD6wNFkh\|ryPLh?=	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
Rosetta2 DE3	MXjGeY5kfGmxbjDhd5NigQ>?		M4XITVMxKG2rboO=		M1Lp[2lvcGmkaYTpc44hd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IHLpcoRqdmdidH:gdoVkd22kaX7hcpQhcHWvYX6gUk11\XKvaX7hcEBJcXN4LYTh[4dm\CCEUlS0JIJzd22xZH;tZYlvKDJiKEOzN{B1dyB2NkCgdoV{cWS3ZYOpJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCIbH;1doV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFc1QCEQvF2u	MnXJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh2NkO0PFcoRjJ6NE[zOFg4RC:jPh?=
THP1	NYCy[JBKSW62aXnu[oxidW2jdH;yfUBie3OjeR?=				MlHNRY51cWmwZnzhcY1ifG:{eTDhZ5Rqfmm2eTDpckBpfW2jbjDUTHAyKGOnbHzz	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN6NkWyPUc,OjJ\|OE[1Nlk9N2F-
HT-29	M3LKb2Z2dmO2aX;uJIF{e2G7	MkLlNE4{OTJ3IIXNJJRwKDVidV2=	MlHSNlQhcHK\|		M{LFS2lvcGmkaYTpc44hd2ZiQmLEOEBqdiCqdX3hckBJXC1{OTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4h[y2PeXOgdJJwfGWrbjDlfJBz\XO\|aX;uJIF1KDBwM{GyOUB2VSC2bzC1JJVOKHWPIHHmeIVzKDJ2IHjyd{BjgSCZZYP0[ZJvKGKub4T0bY5oKG2ndHjv[C=>	NUH2TIRpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1OVk1OjhpPkK1OVU6PDJ6PD;hQi=>
MV4-11	MWnGeY5kfGmxbjDhd5NigQ>?				MXnJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gUXY1NTFzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHTve45z\We3bHH0bY9vKG:oIFLDUFIhWk6DIHX4dJJme3Orb36gZpkhWk6DLYPldUBidmGueYPpdy=>	M1mzVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MkW5O\|UyLz5{OUK1PVc2OTxxYU6=
MV4-11	MnXxSpVv[3Srb36gZZN{[Xl?				MlvWTY5pcWKrdHnvckBw\iCEUlS0JIlvKGi3bXHuJG1XPC1zMTDj[YxteyCjc4Pld5Nm\CCjczDkc5dvemWpdXzheIlwdiCxZjDjUXlEKFKQQTDlfJBz\XO\|aX;uJIJ6KFKQQT3z[ZEh[W6jbInzbZM>	NFfaVGs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK1PVc2OSd-MkmyOVk4PTF:L3G+
U-2 OS	MoLydWhVWyCjc4PhfS=>				NVXZWXlyeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGWtNkBQWyClZXzsdy=>	M1:5VFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673	NYXzcZZmeUiWUzDhd5NigQ>?				MmfqdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEF4N{OgZ4VtdHN?	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
DAOY	M4fDXJFJXFNiYYPzZZk>				NH;DTVByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?=	MkK2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
BT-37	NVTXUmJneUiWUzDhd5NigQ>?				NEHIO3dyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQmStN\|ch[2WubIO=	NH75b4Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	MmPldWhVWyCjc4PhfS=>				MWPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWkRiY3XscJM>	NWDESm9TRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-SH	NWm5e2E6eUiWUzDhd5NigQ>?				M2rpfZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-12	M1zHW5FJXFNiYYPzZZk>				MV;xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	M1jUTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R)	MVvxTHRUKGG\|c3H5				M3jRXZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCPRzC2N{ApPi2WRzDSLUBk\Wyucx?=	NFvZ[5M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB1643	Mk\CdWhVWyCjc4PhfS=>				M3HvU5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQkG2OFMh[2WubIO=	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
OHS-50	NXHzbJdDeUiWUzDhd5NigQ>?				MYPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	M1Ti[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
fibroblast cells	M2mwT5FJXFNiYYPzZZk>				M4H6OpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiClb370do9tKEiqIIfpcIQhfHmyZTDmbYJzd2KuYYP0JINmdGy\|	MlywQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh41	MYPxTHRUKGG\|c3H5				MmfrdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqNEGgZ4VtdHN?	NXPmfpVjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
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SJ-GBM2	MUDxTHRUKGG\|c3H5				NUOxXmtqeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM>	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	NHvOdmlyUFSVIHHzd4F6				NWixS\|RTeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM>	NEnRS2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	Mn7MdWhVWyCjc4PhfS=>				M2DscJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQj3FRoMyKGOnbHzz	MnLaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
LAN-5	NGrlOJNyUFSVIHHzd4F6				NE[3UXJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO=	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh18	NY\MbI9IeUiWUzDhd5NigQ>?				M2XBNZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEG4JINmdGy\|	M1:wbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot

α-SMA / Fibronectin / Collagen-1 ; FoxM1 / AURKB / Survivin / cyclin B / PLK1 ; HP1α / HP1β / HP1γ

27732564 26877780 30386240

In vivo

Administration of I-BET151 at 30 mg/kg/day significantly inhibits tumor growth of murine MLL-AF9 and human MLL-AF4 leukaemia in mice, and provides marked survival benefit. ^[1]

Protocol (from reference)

Kinase Assay: ^[1]	Fluorescence anisotropy (FP) ligand displacement assay: All components are dissolved in buffer of composition 50 mM HEPES pH 7.4, 150 mM NaCl and 0.5 mM CHAPS with final concentrations of BRD 2/3/4 75 nM, fluorescent ligand 5 nM. 10 μL of this reaction mixture is added using a micro multidrop to wells containing 100 nL of various concentrations of I-BET151 or DMSO vehicle (1% final) in Greiner 384 well Black low volume microtitre plate and equilibrated in the dark for 60 minutes at room temperature. Fluorescence anisotropy is read in Envision (lex = 485 nm, lEM = 530 nm; Dichroic = 505 nM).
Cell Research: ^[1]	Cell lines: MV4;11, MOLM13, NOMO1, RS4;11, HEL, HL60 and K562 Concentrations: Dissolved in DMSO, final concentrations ~100 μM Incubation Time: 24, or 72 hours Method: Cells are exposed to various concentrations of I-BET151 for 24 or 72 hours in 384-well or 96-well plates. For cell growth inhibition assays, plates are added with CellTiter-Glo reagent using a volume equivalent to the cell culture volume in the wells, shaken for approximately 2 minutes and chemiluminescent signal is read on the Analyst GT or EnVision Plate Reader. For cell proliferation assays, CellTiter-Aqueous One is added to each well and plates are incubated for 4 hours at 37 °C. Absorbance is read at 490 nm on a SpectraMax Gemini reader
Animal Research: ^[1]	Animal Models: NOD-SCID mice injected intravenously with MV4;11 cells, and C57BL/6 mice injected intravenously with MLL-AF9 cells Dosages: ~30 mg/kg/day Administration: Intraperitoneal injection

References

[1] Dawson MA, et al. Nature, 2011, 478(7370), 529-533.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	415.44
Formula	C₂₃H₂₁N₅O₃
CAS No.	1300031-49-5
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC1=C(C(=NO1)C)C2=C(C=C3C(=C2)N=CC4=C3N(C(=O)N4)C(C)C5=CC=CC=N5)OC

Download I-BET151 (GSK1210151A) 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:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

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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Dilution Calculator Molecular Weight Calculator

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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