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I-BET151 (GSK1210151A)

Name: I-BET151 (GSK1210151A)
Brand: Selleck Chemicals
SKU: S2780
Rating: 5 (35 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 35 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	M{DVNYN6fG:2b4jpZ4l1gSCjc4PhfS=>	NF\oUll,OTByIN88US=>		M{D5eWROW09?	MUPJR\|UxRTJ4IH7N	NWfqdHJ7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
RS4;11	MmDpZ5l1d3SxeHnjbZR6KGG\|c3H5	NV3IW5hqhjFyMDFOwG0>		Ml;MSG1UVw>?	M1e3[WlEPTB;MUmyJI5O	NH\6SoY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
MOLM13	M3\MN4N6fG:2b4jpZ4l1gSCjc4PhfS=>	M4HodZ4yODBizszN		MYLEUXNQ	MlXyTWM2OD1zMkCgcm0>	NHnrTGU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
NOMO1	NYHHXJA1[3m2b4TvfIlkcXS7IHHzd4F6	MkK1glExOCEQvF2=		NXT1WpZXTE2VTx?=	Mm\rTWM2OD1zNTDuUS=>	NFfCVXc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
HEL	NIXHV2NkgXSxdH;4bYNqfHliYYPzZZk>	MUH+NVAxKM7:TR?=		NIr6b\|JFVVOR	MXPJR\|UxRTFizszN	M1KwOFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
K562	NUjxW29K[3m2b4TvfIlkcXS7IHHzd4F6	NWGzVWdJhjFyMDFOwG0>		M3\0SWROW09?	NEn3WJNKSzVyPkGwNEDPxE1?	MlvqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
MEG01	M2j2NIN6fG:2b4jpZ4l1gSCjc4PhfS=>	NHruTZR,OTByIN88US=>		MnjhSG1UVw>?	NXS1[4lJUUN3ME2yOUDPxE1?	M13rSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
HL60	NGOzenlkgXSxdH;4bYNqfHliYYPzZZk>	MWf+NVAxKM7:TR?=		M1\Tb2ROW09?	M3;YdGlEPTB;OEmwJI5O	NGTEepo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
MV4;11	MkPsRZBweHSxc3nzJIF{e2G7	NF61Zld,OTByIN88US=>		NVfKXmJGTE2VTx?=	M4fUR4lv\HWlZYOgZZBweHSxc3nz	M{SyZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
MOLM13	MWfBdI9xfG:\|aYOgZZN{[Xl?	M2\YN54yODBizszN		M3Lz[2ROW09?	NHzxfGlqdmS3Y3XzJIFxd3C2b4Ppdy=>	NF;mVoU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUm2OFM1OCd-MkG5OlQ{PDB:L3G+
MV4;11	M2fKdWZ2dmO2aX;uJIF{e2G7			MmHpSG1UVw>?	MV;k[YNz\WG\|ZYOgeIhmKHKnY4L1bZRu\W62IH;mJGJTTDNxNDDhcoQhcW2yYXny[YQhemWlcoXpeI1mdnRib3[gR2RMQSCjbnSgVGFHOSC2bzD0bIUhfHKjboPjdolxfGmxbnHsJJN1[XK2IIPpeIU>	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
PBMC	MXrGeY5kfGmxbjDhd5NigQ>?			NYrBd\|ZoTE2VTx?=	MWHpcohq[mm2czDJUE03KHerdHigdGlEPTBib3[gOk44	NFzH[449[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkSzO\|EyPSd-MkK0N\|cyOTV:L3G+
A2	NHHCWWFHfW6ldHnvckBie3OjeR?=	NGDme4d,OTBizszN		Mlr5SG1UVw>?	NXPPUGlQemWjY4TpeoF1\XNibHH0[Y51KEiLVj2x	NWHLe451RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyOVUzOThpPkKzNlU2OjF6PD;hQi=>
A72	MWTGeY5kfGmxbjDhd5NigQ>?	M{\UfJ4yOCEQvF2=		MmHISG1UVw>?	MVXy[YFkfGm4YYTld{Bt[XSnboSgTGlXNTF?	NIfX[IQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K1OVIyQCd-MkOyOVUzOTh:L3G+
BC1	NXH6d3JOT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	Mlq5glEh\|ryP		M1H6TGROW09?	M4TVZmlEPTB;MkKwJI5O	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC3	NYL5bm1HT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MWn+NUDPxE1?		M1zBWmROW09?	NFTvcYtKSzVyPUS2NEBvVQ>?	NHjHV4Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BCBL1	M2Dsb2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M1fCRp4yKM7:TR?=		MkfGSG1UVw>?	MXzJR\|UxRTN\|MDDuUS=>	M{O5[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BJAB	MorYS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NGjUepV,OSEQvF2=		MX3EUXNQ	M2DMN2lEPTB;OUewJI5O	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
Namalwa	M{K5XWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M4LlcJ4yKM7:TR?=		NXrFW4dYTE2VTx?=	NX3w[oZ1UUN3ME25O\|Ahdk1?	Mki3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5OUK0OFgoRjJ\|N{myOFQ5RC:jPh?=
Jurkat	MmW3S5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NFPhe2l,OSEQvF2=		MlzmSG1UVw>?	NYHSZ2ZoUUN3ME2xNlIxKG6P	NXvuSIJ4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
MM1S	NXHoSnNWT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MmfIglEh\|ryP		NGn6[WlFVVOR	Ml64TWM2OD15NkCgcm0>	NEO5WVU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
U266	M1\4b2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M{HNbZ4yKM7:TR?=		NUDuN3ZyTE2VTx?=	NH7LXlVKSzVyPUm1NEBvVQ>?	M3j3O\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
UM-PEL-1	NVrJXIx1T3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NHrpO\|V,OSEQvF2=		M2nKXWROW09?	MV\JR\|UxRTJzMDDuUS=>	NHXxXlM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
UM-PEL-3	M{L4[Wdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M{Tkbp4yKM7:TR?=		NYnFXGtETE2VTx?=	MVLJR\|UxRTF6MDDuUS=>	M3OyRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BC1	NVvNNlRNTnWwY4Tpc44h[XO\|YYm=	MlLIOVAxKG6P		NGDvUWFFVVOR	NX[ye2lzcW6mdXPld{Bk\WyuLXP5Z4xmKGG{cnXzeC=>	NFzJOG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BC3	NULlOYFjTnWwY4Tpc44h[XO\|YYm=	Ml;COVAxKG6P		Ml;WSG1UVw>?	NFnIV\|RqdmS3Y3XzJINmdGxvY4njcIUh[XK{ZYP0	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC1	MYPGeY5kfGmxbjDhd5NigQ>?	NITvcnE5ODBibl2=		MV;EUXNQ	NHXLN2tz\WS3Y3XzJIMuVXmlIIDyc5RmcW5ibHX2[Yx{	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BC3	M4nBcWZ2dmO2aX;uJIF{e2G7	MoHKPFAxKG6P		NGj3UJZFVVOR	MlzsdoVlfWOnczDjMW16[yCycn;0[YlvKGyndnXsdy=>	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
H929	M2jES2Z2dmO2aX;uJIF{e2G7	MVH+NUDPxE1?		NXrQbIo4TE2VTx?=	MnP6bY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	NFfOUXE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS12PE	NYn6SXJQTnWwY4Tpc44h[XO\|YYm=	M4XvW54yKM7:TR?=		M3jnO2ROW09?	NFHXSndqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS12BM	MVjGeY5kfGmxbjDhd5NigQ>?	MWn+NUDPxE1?		NEP6e5VFVVOR	Ml21bY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	NHX6OVc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS18	NFS0[nRHfW6ldHnvckBie3OjeR?=	MVf+NUDPxE1?		MUnEUXNQ	MXTpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	M4fQWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS11	MUnGeY5kfGmxbjDhd5NigQ>?	Mmm5glEh\|ryP		MXTEUXNQ	MWnpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	NGKwbXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
RPMI8226	MkjFSpVv[3Srb36gZZN{[Xl?	M33iS54yKM7:TR?=		NGPQOXhFVVOR	NEPPPZhqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
H929	NGTKUZJCeG:ydH;zbZMh[XO\|YYm=	MWf+NUDPxE1?		MlL6SG1UVw>?	M{DLWIlv\HWlZYOgZ4VtdCCjcH;weI9{cXN?	M3WxfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS12PE	NHjkSIRCeG:ydH;zbZMh[XO\|YYm=	MnSyglEh\|ryP		NYfScW1ZTE2VTx?=	MlfubY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?	M1\VclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS12BM	M2nkTGFxd3C2b4Ppd{Bie3OjeR?=	MkP4glEh\|ryP		MYPEUXNQ	NHTENlBqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	NWjCVnk5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS18	NHL0U2FCeG:ydH;zbZMh[XO\|YYm=	MYP+NUDPxE1?		M4DPfWROW09?	NF7RN4ZqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	M4f2VVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS11	NFzqUJJCeG:ydH;zbZMh[XO\|YYm=	MlXOglEh\|ryP		NUDqPGNHTE2VTx?=	NHrHdlBqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	NYSz[FdHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
RPMI8226	M3\aVGFxd3C2b4Ppd{Bie3OjeR?=	MWL+NUDPxE1?		NH;L[oZFVVOR	MmnHbY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
U87MG	NX3OTJRnTnWwY4Tpc44h[XO\|YYm=	Mnv4glExKM7:TR?=		Mlf6SG1UVw>?	MVLy[YR2[2W\|IGW4O21IKGOnbHz1cIFzKEGWUDD3bZRpKEmFNUCgc4YhOS5yNTFOwG0>	Mn\zQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OU[zPFEoRjJ2NEm2N\|gyRC:jPh?=
A172	MWXGeY5kfGmxbjDhd5NigQ>?	MXH+NVAh\|ryP		NYixUYh6TE2VTx?=	MVfy[YR2[2W\|IHPlcIx2dGG{IFHUVEB4cXSqIFnDOVAhd2ZiMT6yPEDPxE1?	M{G3[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEm2N\|gyLz5{NES5OlM5OTxxYU6=
SW1783	NHLSWWRHfW6ldHnvckBie3OjeR?=	M1PzS54yOCEQvF2=		NVvldFRVTE2VTx?=	NGG5RoZz\WS3Y3XzJINmdGy3bHHyJGFVWCC5aYToJGlEPTBib3[gNk43QCEQvF2=	MmjZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OU[zPFEoRjJ2NEm2N\|gyRC:jPh?=
U87MG	NYjrSHFzTnWwY4Tpc44h[XO\|YYm=	MUT+NVAh\|ryP		M4fEZWROW09?	NVTPVlFWcW6lcnXhd4V{KHC{b4DvdpRqd25ib3[gZ4VtdHNiaX6geIhmKEdzL2OgeJJidnOrdHnvci=>	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR7NkO4NUc,OjR2OU[zPFE9N2F-
RAW267.4	NXH5S5ZSTnWwY4Tpc44h[XO\|YYm=	NX3QN2NmOSEQvF2=		NGLZeI1FVVOR	MlrodoVlfWOnczDJUE03KHC{b3T1Z5Rqd25iaX7keYNm\CCkeTDMVHM>	NUKxS5hTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4OVkxODhpPkK0PFU6ODB6PD;hQi=>
RAW267.4	NY\mO3dXTnWwY4Tpc44h[XO\|YYm=	MlfPNUDPxE1?		NX\Xb4s3TE2VTx?=	NYLIbnUyemWmdXPld{B1cGViYYPzc4Nq[XSrb36gZoV1f2WnbjDCVmQ1KGGwZDDhZ4V1gWyjdHXkJJA3PQ>?	MkjJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6NUmwNFgoRjJ2OEW5NFA5RC:jPh?=
Me007	MkDVS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MkGxglExOCEQvF2=		MUHEUXNQ	MYDpcohq[mm2czD0bIUh\3Kxd4To	MnHWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
SK-Mel-28	NUm3TpNqT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NXfoblR4hjFyMDFOwG0>		MmnjSG1UVw>?	MVvpcohq[mm2czD0bIUh\3Kxd4To	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RMU	M2jRO2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M2T6PZ4yODBizszN		MnfISG1UVw>?	M{e1N4lvcGmkaYTzJJRp\SCpcn;3eIg>	NVvzZZF1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-JD	M2\Tc2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NHvnZpd,OTByIN88US=>		M3XaS2ROW09?	Ml7rbY5pcWKrdIOgeIhmKGe{b4f0bC=>	NYLNTYZORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RM	NFrrZW9Iem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MWr+NVAxKM7:TR?=		NIC4RVFFVVOR	M3f2WolvcGmkaYTzJJRp\SCpcn;3eIg>	M{HCSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Me007	NULyT\|J4SXCxcITvd4l{KGG\|c3H5	MmTkglExOCEQvF2=		MYrEUXNQ	NYnYOFQ2cW6mdXPld{BieG:ydH;zbZM>	M1W1[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
SK-Mel-28	MX3BdI9xfG:\|aYOgZZN{[Xl?	MnLCglExOCEQvF2=		NFzTOYZFVVOR	MYDpcoR2[2W\|IHHwc5B1d3Orcx?=	M4Tu[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	NXey[ZFCSXCxcITvd4l{KGG\|c3H5	MoPrglExOCEQvF2=		M2C0RmROW09?	NXX6cIZ7cW6mdXPld{BieG:ydH;zbZM>	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-JD	NXzrVFVWSXCxcITvd4l{KGG\|c3H5	MVz+NVAxKM7:TR?=		M3TLd2ROW09?	NIHJPIxqdmS3Y3XzJIFxd3C2b4Ppdy=>	NH;uc\|E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RM	MlzXRZBweHSxc3nzJIF{e2G7	MkHBglExOCEQvF2=		NGSxdpRFVVOR	MXfpcoR2[2W\|IHHwc5B1d3Orcx?=	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Me007	NYDXSmhLTnWwY4Tpc44h[XO\|YYm=	NH3TOG4yOCEQvF2=		NXnWUG96TE2VTx?=	NHuwPVFqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIJ6KHWycnXneYxifGmxbjDv[kBxOjF?	NXnRVWt{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
SK-Mel-28	NID3O4RHfW6ldHnvckBie3OjeR?=	M3GyelExKM7:TR?=		M{fNNGROW09?	NIP1N\|lqdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIJ6KHWycnXneYxifGmxbjDv[kBxOjF?	NEW5[HE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RMU	NWTobZRYTnWwY4Tpc44h[XO\|YYm=	Mlq0NVAh\|ryP		MkHiSG1UVw>?	M{CzXIlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	NH:wR2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-JD	MmP3SpVv[3Srb36gZZN{[Xl?	NHLzWmIyOCEQvF2=		MXnEUXNQ	M4jsT4lv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	NHf0W2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RM	MoS3SpVv[3Srb36gZZN{[Xl?	M3O0fVExKM7:TR?=		MVfEUXNQ	Mm[wbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dDDifUB2eHKnZ4XsZZRqd25ib3[gdFIy	Mn7GQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Me007	NUO3SmVSTnWwY4Tpc44h[XO\|YYm=	NXfDNJJjOTBizszN		MVfEUXNQ	NG\tSHF2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
SK-Mel-28	NU\kVYdqTnWwY4Tpc44h[XO\|YYm=	Ml;zNVAh\|ryP		NV3WdGFtTE2VTx?=	NIrLOZN2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	NUPxSG1tRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RMU	NIfIO4FHfW6ldHnvckBie3OjeR?=	M4jHcVExKM7:TR?=		M2HvbGROW09?	NYq0coMzfXC{ZXf1cIF1\XNicILvZZBweHSxdHnjJIFv\CClZXzsJIN6[2ynIHHydoV{fCCpZX7ldy=>	Mnv1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-JD	MUfGeY5kfGmxbjDhd5NigQ>?	M3X4c\|ExKM7:TR?=		M1fJWGROW09?	MmXIeZBz\We3bHH0[ZMheHKxYYDvdJRwfGmlIHHu[EBk\WyuIHP5Z4xmKGG{cnXzeEBo\W6ncx?=	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RM	NVnXc2JyTnWwY4Tpc44h[XO\|YYm=	MnO2NVAh\|ryP		MlzuSG1UVw>?	Mon4eZBz\We3bHH0[ZMheHKxYYDvdJRwfGmlIHHu[EBk\WyuIHP5Z4xmKGG{cnXzeEBo\W6ncx?=	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
HepG2	MYHGeY5kfGmxbjDhd5NigQ>?		NW[2Z5FIOThiaILz		NGr5Z4JWeHKnZ4XsZZRqd25ib3[gRZBwSTFiZYjwdoV{e2mxbjDpckBpfW2jbjDI[ZBIOiClZXzsd{Bie3Onc4Pl[EBieyClb37j[Y51emG2aX;uJJJmeXWrcnXkJJRwKGmwY4LlZZNmKDdyJTDv[kBtfWOrZnXyZZNmKGGldHn2bZR6KGGodHXyJFE5KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFXDNVcxKD1iMD6wPUDPxE1w	NImxTY89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO4OlUzQSd-MkKzPFY2Ojl:L3G+
Raji	NGXrZnlHfW6ldHnvckBie3OjeR?=		NVrxNlhSPCCqcoO=		MWnJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gVoFrcSClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gUXlEKGW6cILld5Nqd25iYX\0[ZIhPCCqcoOsJGlEPTBiPTCwMlE{KM7:TT6=	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMEe1PEc,OjR7MEC3OVg9N2F-
MV4-11	MYfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		M{\BNVczKGi{cx?=		NFrwbnZIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBOXjRvMUGgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NEA:KDBwMUG5JO69VS5?	M2nYUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUW5OFI5Lz5{NUW1PVQzQDxxYU6=
MM1S	M2jnTWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MVe3NkBpenN?		MYDHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDNUVFUKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDTVmIh[XO\|YYmsJGlEPTBiPTCwMlI6QSEQvF2u	NFqxUoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUW1PVQzQCd-MkW1OVk1Ojh:L3G+
HT-29	NEC2[GlIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		NUPBRZVYPzJiaILz		MVnHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDIWE0zQSClZXzsd{Bi\nSncjC3NkBpenNiYomgV3JDKGG\|c3H5MEBKSzVyIE2gNE46PDVizszNMi=>	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTV3OUSyPEc,OjV3NUm0Nlg9N2F-
Rosetta2 DE3	MlH1SpVv[3Srb36gZZN{[Xl?		NVPhNGs2OzBibXnudy=>		MUfEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGNDDCSFEhMDR2IITvJFE3QCCjbXnuc{Bi[2mmIILld4llfWW\|KTCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDJR\|UxKD1iMD6wN\|E4KM7:TT6=	NV;He4tCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
MV4-11	NIL6N3ZEgXSxdH;4bYNqfHliYYPzZZk>		M13vSlQh\GG7cx?=		MUnDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNWlQuOTFiY3XscJMhcGG{Yn;ybY5oKE2OTEGg[pV{cW:wIHflcoUh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPCCmYYnzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[XO\|YYmsJGlEPTBiPTCwMlE3OiEQvF2u	M1XCc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MWnGeY5kfGmxbjDhd5NigQ>?		NYL4VpVEOzBibXnudy=>		NHXjboZFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEOEBDTDJiKEOzN{B1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvOjJ4IN88UU4>	NFPC[GE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
MOLM13	M3\2N2N6fG:2b4jpZ4l1gSCjc4PhfS=>		NV;KUJN{PCCmYYnz		M3S0VmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1QVE1zMzDj[YxteyCqYYLic5JqdmdiTVzMNUBnfXOrb36g[4Vv\SCjc4Pld5Nm\CCjczDndo94fGhiaX7obYJqfGmxbjDh[pRmeiB2IHThfZMh[nliQ3XscHRqfGW{LVfsc{BtfW2rbnXzZ4VvfCCjc4PhfUwhUUN3MDC9JFAvOjJ6IN88UU4>	NXPT[HpCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	M2Lkc2Z2dmO2aX;uJIF{e2G7		NXTPSFVuOzBibXnudy=>		NXnoT4c3UW6qaXLpeIlwdiCxZjDGRW0udGGkZXzl[EBbSkF{NEigZolv\GmwZzD0c{Bz\WOxbXLpcoFvfCCqdX3hckBPNXSncn3pcoFtKEirc{[teIFo\2WmIFLSSFQh[nKxbX;kc41icW5iMTCoOFQhfG9iMU[4JJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvODNzNzFOwG0v	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
MV4-11	MVPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		M{\QeVQh\GG7cx?=		NVjodnR3T3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVVZ2LUGxJINmdGy\|IHHmeIVzKDRiZHH5d{BjgSCZU2StPEBie3OjeTygTWM2OCB;IECuNVYzKM7:TT6=	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
Rosetta2 DE3	NHXYT2dHfW6ldHnvckBie3OjeR?=		NYr5OnNHOzBibXnudy=>		NETSe4dKdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiB{IDizN\|MhfG9iNE[wJJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvOjJ4IN88UU4>	NVXuV5ZnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
MOLM13	NXHjV2JoT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		M17FOFQh\GG7cx?=		NWewWXRjT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVU:OTUGzJINmdGy\|IHHmeIVzKDRiZHH5d{BjgSCZU2StPEBie3OjeTygTWM2OCB;IECuNlI5KM7:TT6=	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
Rosetta2 DE3	MoXYSpVv[3Srb36gZZN{[Xl?				MY\CbY5lcW6pIHHm[olvcXS7IITvJIJqd3SrbonsZZRm\CCEUlSzJGJFOSBqMkSgeI8hOTR2IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCkeTDibY8udGG7ZYKgbY51\XKoZYLvcYV1enlibXX0bI9lNCCNZDC9JFAvODJ7ODFOwG0v	NFvWTYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	NWLJPIVbTnWwY4Tpc44h[XO\|YYm=				NV:1eYpVSmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgRnJFOyCEREKgLFMxPiC2bzC0NVch[W2rbn:gZYNq\CC{ZYPp[JVmeyliKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gVo9{\XS2YUKgSGU{KGOnbHzzJIJ6KGKrbz3sZZlmeiCrboTldoZmem:vZYTyfUBu\XSqb3SsJGtlKD1iMD6wOFA2KM7:TT6=	NX;p[4tsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	MWnGeY5kfGmxbjDhd5NigQ>?				MWTCbY5lcW6pIHHm[olvcXS7IITvJIJqd3SrbonsZZRm\CCEUlS0JGJFOSBqNESgeI8hOTZ6IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCkeTDibY8udGG7ZYKgbY51\XKoZYLvcYV1enlibXX0bI9lNCCNZDC9JFAvODV{ODFOwG0v	NX:yNpk5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	MlHLSpVv[3Srb36gZZN{[Xl?				MXTCbY5lcW6pIHHm[olvcXS7IITvJIJqd3SrbonsZZRm\CCEUlSyJGJFOSBqN{KgeI8hOjB3IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCkeTDibY8udGG7ZYKgbY51\XKoZYLvcYV1enlibXX0bI9lNCCNZDC9JFAvODV2ODFOwG0v	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	MljmSpVv[3Srb36gZZN{[Xl?				NXzYcnNCSmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgRnJFOiCEREKgLFM1QSC2bzC0OlAh[W2rbn:gZYNq\CC{ZYPp[JVmeyliKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gVo9{\XS2YUKgSGU{KGOnbHzzJIJ6KGKrbz3sZZlmeiCrboTldoZmem:vZYTyfUBu\XSqb3SsJGtlKD1iMD6wO\|A{KM7:TT6=	NGPSeI09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	NX3oOpF2TnWwY4Tpc44h[XO\|YYm=				NWDzNG5rSmmwZHnu[{Bi\m[rbnn0fUB1dyCkaX;0bY56dGG2ZXSgRnJFPCCEREKgLFM{OyC2bzC0OlAh[W2rbn:gZYNq\CC{ZYPp[JVmeyliKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gVo9{\XS2YUKgSGU{KGOnbHzzJIJ6KGKrbz3sZZlmeiCrboTldoZmem:vZYTyfUBu\XSqb3SsJGtlKD1iMD6yNVUh\|ryPLh?=	MnXjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	M2K1SmZ2dmO2aX;uJIF{e2G7				MlLsRolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQ2LFRmJRKChzMESzJJRwKDFzNUmgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOy5yOESg{txONg>?	M2j1PFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	NHz0XppHfW6ldHnvckBie3OjeR?=		M{PpPVMxKG2rboO=		NGToRYFFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEN{BDTDFiKEK0JJRwKDF2NDDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFA4OiEQvF2u	NEfyT4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	NHTOdpVHfW6ldHnvckBie3OjeR?=		MWWzNEBucW6\|		NYjPeFczTGm\|cHzhZ4Vu\W62IH;mJGZCVS2uYXLlcIVlKFqEQUK0PEBnem:vIFLSSFQhSkRzIDi0OEB1dyBzNkigZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlAxQSEQvF2u	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	NXGwUWJXTnWwY4Tpc44h[XO\|YYm=		NUO2e4RtOzBibXnudy=>		MXnEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGMjDCSFEhMDd{IITvJFIxPSCjbXnuc{Bi[2mmIILld4llfWW\|KTCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDLbUA:KDBwMEC5JO69VS5?	NYG5eYZmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	NIXI[5hHfW6ldHnvckBie3OjeR?=		NVO0Vm4yOzBibXnudy=>		NUTzTnJZTGm\|cHzhZ4Vu\W62IH;mJGZCVS2uYXLlcIVlKFqEQUK0PEBnem:vIFLSSFMhSkR{IDizNFYhfG9iNEG3JIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDh[pRmeiB\|MDDtbY5{KGK7IH\seY9z\XOlZX7j[UBxd2yjcnn6ZZRqd25iYYPzZZktKEurIE2gNE4xOjJ\|IN88UU4>	M124fFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	M{e2V2Z2dmO2aX;uJIF{e2G7		MW[zNEBucW6\|		MXfEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGMjDCSFIhMDN2OTD0c{A1PjBiYX3pco8h[WOrZDDy[ZNq\HWnczmgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hWm:\|ZYT0ZVIhTEV\|IHPlcIx{KGGodHXyJFMxKG2rboOgZpkh\my3b4Lld4NmdmOnIIDvcIFzcXqjdHnvckBie3OjeTygT4khRSByLkC0PVYh\|ryPLh?=	MkXZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	MVnGeY5kfGmxbjDhd5NigQ>?		MYOzNEBucW6\|		NYC0VnZTTGm\|cHzhZ4Vu\W62IH;mJGZCVS2uYXLlcIVlKFqEQUK0PEBnem:vIFLSSFQhSkR{IDizN\|MhfG9iNE[wJIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDh[pRmeiB\|MDDtbY5{KGK7IH\seY9z\XOlZX7j[UBxd2yjcnn6ZZRqd25iYYPzZZktKEurIE2gNE4xPzR6IN88UU4>	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	MXPGeY5kfGmxbjDhd5NigQ>?		MXmzNEBucW6\|		M1\6[mlvcGmkaYTpc44hd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IHLpcoRqdmdidH:gdoVkd22kaX7hcpQhcHWvYX6gUk11\XKvaX7hcEBJcXN4LYTh[4dm\CCEUlS0JIJzd22xZH;tZYlvKDFiKES0JJRwKDF4ODDy[ZNq\HWnczmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KE[ub4Xy[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGtqKD1iMD6wNFkh\|ryPLh?=	M2r0[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6NE[zOFg4Lz5{OES2N\|Q5PzxxYU6=
Rosetta2 DE3	MoDVSpVv[3Srb36gZZN{[Xl?		M4\B[\|MxKG2rboO=		NIfXO\|BKdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiB{IDizN\|MhfG9iNE[wJJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlA4PDhizszNMi=>	NXLmVpA1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
THP1	M3vNWWFvfGmrbn\sZY1u[XSxcomgZZN{[Xl?				MXnBcpRqcW6obHHtcYF1d3K7IHHjeIl3cXS7IHnuJIh2dWGwIGTIVFEh[2WubIO=	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN6NkWyPUc,OjJ\|OE[1Nlk9N2F-
HT-29	NYXLfnA6TnWwY4Tpc44h[XO\|YYm=	M1rITFAvOzF{NTD1UUB1dyB3IIXN	MWqyOEBpenN?		MkTUTY5pcWKrdHnvckBw\iCEUlS0JIlvKGi3bXHuJGhVNTJ7IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBkNU27YzDwdo91\WmwIHX4dJJme3Orb36gZZQhOC5\|MUK1JJVOKHSxIEWgeW0hfU1iYX\0[ZIhOjRiaILzJIJ6KFenc4Tldo4h[myxdITpcochdWW2aH;k	M2DwTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUW5OFI5Lz5{NUW1PVQzQDxxYU6=
MV4-11	NV;QUVM2TnWwY4Tpc44h[XO\|YYm=				M1fWZ2lvcGmkaYTpc44hd2ZiQmLEOEBqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOg[I94dnKnZ4XsZZRqd25ib3[gRmNNOiCUTlGg[ZhxemW\|c3nvckBjgSCUTlGtd4VyKGGwYXz5d4l{	NEj1ZXg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK1PVc2OSd-MkmyOVk4PTF:L3G+
MV4-11	NGr0TppHfW6ldHnvckBie3OjeR?=				M{nOO2lvcGmkaYTpc44hd2ZiQmLEOEBqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOg[I94dnKnZ4XsZZRqd25ib3[gZ21[SyCUTlGg[ZhxemW\|c3nvckBjgSCUTlGtd4VyKGGwYXz5d4l{	NXv0UIdWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyOVk4PTFpPkK5NlU6PzVzPD;hQi=>
U-2 OS	MVXxTHRUKGG\|c3H5				M{nnN5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCXLUKgU3Mh[2WubIO=	NUX3[oxWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673	NI\rSG1yUFSVIHHzd4F6				MYPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSTZ5MzDj[Yxtew>?	NGHNeXI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
DAOY	NIraenlyUFSVIHHzd4F6				NITxbIFyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?=	M17hSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-37	NHzue\|NyUFSVIHHzd4F6				MnzCdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy\|	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
RD	MVrxTHRUKGG\|c3H5				NFjYd5lyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUlSgZ4VtdHN?	NHr4fmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-SH	NFPkc2hyUFSVIHHzd4F6				M{nQ[JFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	NULPeYxzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-12	NWDocFJZeUiWUzDhd5NigQ>?				NWXXNGVXeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFLUMVEzKGOnbHzz	MoP5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R)	MYXxTHRUKGG\|c3H5				M1vq[5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCPRzC2N{ApPi2WRzDSLUBk\Wyucx?=	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB1643	MkC0dWhVWyCjc4PhfS=>				M4G5N5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQkG2OFMh[2WubIO=	NHrvTnc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	MXnxTHRUKGG\|c3H5				NWTpdVJmeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
fibroblast cells	NGDITnByUFSVIHHzd4F6				MmHxdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKGOxboTyc4whUGhid3ns[EB1gXCnIH\pZpJw[myjc4SgZ4VtdHN?	M1rvTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh41	NILV[VdyUFSVIHHzd4F6				Mn;5dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqNEGgZ4VtdHN?	NFn5d5U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh30	MYnxTHRUKGG\|c3H5				NXf2XJVkeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoN\|Ah[2WubIO=	NI\TcpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SJ-GBM2	MUnxTHRUKGG\|c3H5				MVzxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	MlzDdWhVWyCjc4PhfS=>				M3r3c5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz	NH7vfIQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	Mn7udWhVWyCjc4PhfS=>				MXnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	M3fSdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	NW\4Z497eUiWUzDhd5NigQ>?				NFjjTGNyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO=	MkHuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh18	MWrxTHRUKGG\|c3H5				MUfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>?	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-

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 (Only for Reference)
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 (Only for Reference)

References

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

Solubility (25°C)

In vitro	Ethanol	27 mg/mL (64.99 mM)
	DMSO	Insoluble
	Water	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight	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
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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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