I-BET151 (GSK1210151A)

Name: I-BET151 (GSK1210151A)
Brand: Selleck Chemicals
SKU: S2780
Rating: 5 (33 reviews)

For research use only.

Catalog No.S2780

33 publications

I-BET151 (GSK1210151A) Chemical Structure

CAS No. 1300031-49-5

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.

Selleck's I-BET151 (GSK1210151A) has been cited by 33 publications

Cell, 2019, 36(2):179-193

PubMed: 28162770 ( click the link to review the publication )

Cancer Cell, 2019, 36(2):179-193

PubMed: 31378681 ( click the link to review the publication )

Cancer Cell, 2018, 34(6):922-938

PubMed: 30537514 ( click the link to review the publication )

Cancer Cell, 2018, 33(3):401-416

PubMed: 29533782 ( click the link to review the publication )

Cancer Discov, 2017, 7(3):302-321

PubMed: 28108460 ( click the link to review the publication )

Nat Commun, 2021, 12(1):1045

PubMed: 33594072 ( click the link to review the publication )

J Clin Endocrinol Metab, 2021, dgaa986

PubMed: 33417713 ( click the link to review the publication )

Genome Biol, 2020, 21(1):269

PubMed: 33143730 ( click the link to review the publication )

Nat Commun, 2020, 14;11(1):1833

PubMed: 32286255 ( click the link to review the publication )

Int J Cancer, 2020, 10.1002/ijc.33000

PubMed: 32249419 ( click the link to review the publication )

Genomics Inform, 2020, 18(4):e37

PubMed: 33412753 ( click the link to review the publication )

J Mol Cell Biol, 2020, 11;12(5):359-371

PubMed: 31565729 ( click the link to review the publication )

Aging (Albany NY), 2020, 12(5):4547-4557

PubMed: 32163373 ( click the link to review the publication )

Cytotherapy, 2020, S1465-3249(20)30929-4

PubMed: 33246884 ( click the link to review the publication )

Int J Oncol, 2020, 56(6):1429-1441

PubMed: 32236593 ( click the link to review the publication )

Genome Med, 2020, 12(1):63

PubMed: 32669118 ( click the link to review the publication )

Clin Transl Med, 2020, 10(6):e181

PubMed: 33135348 ( click the link to review the publication )

EBioMedicine, 2019, 43:201-210

PubMed: 30975544 ( click the link to review the publication )

Epigenetics, 2019, 10.1080/15592294.2019.1656156

PubMed: 31423932 ( click the link to review the publication )

Nat Biomed Eng, 2018, 2(8):578-588

PubMed: 31015631 ( click the link to review the publication )

Mol Cell, 2018, 72(2):341-354

PubMed: 30270106 ( click the link to review the publication )

Nat Commun, 2018, 9(1):5378

PubMed: 30568163 ( click the link to review the publication )

Cancer Res, 2018, 78(2):572-583

PubMed: 29180474 ( click the link to review the publication )

J Immunol, 2018, 201(9):2744-2752

PubMed: 30249811 ( click the link to review the publication )
Sci Rep, 2018, 8(1):3521

PubMed: 29476067 ( click the link to review the publication )

Front Pharmacol, 2018, 9:1166

PubMed: 30386240 ( click the link to review the publication )

Cell Tissue Res, 2018, 374(3):577-585

PubMed: 30182276 ( click the link to review the publication )

Nat Commun, 2017, 8:14802

PubMed: 28378740 ( click the link to review the publication )

Nucleic Acids Res, 2017, 45(14):8403-8410

PubMed: 28854735 ( click the link to review the publication )

Mol Cancer Res, 2017, 15(9):1221-1229

PubMed: 28592703 ( click the link to review the publication )

Theranostics, 2016, 6(2):219-30

PubMed: 26877780 ( click the link to review the publication )

J Hematol Oncol, 2016, 9(1):134

PubMed: 27903272 ( click the link to review the publication )

Oncotarget, 2016, 7(3):2545-54

PubMed: 26575423 ( click the link to review the publication )

Purity & Quality Control

Choose Selective Epigenetic Reader Domain Inhibitors

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	M1T4ZYN6fG:2b4jpZ4l1gSCjc4PhfS=>	M1;ndJ4yODBizszN		NFPNUndFVVOR	NGe0[mpKSzVyPUK2JI5O	MlLzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
RS4;11	NIr5dI9kgXSxdH;4bYNqfHliYYPzZZk>	M1jKPJ4yODBizszN		NXnTSW9oTE2VTx?=	NF\tdJBKSzVyPUG5NkBvVQ>?	NWHKWlk2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
MOLM13	M1PjN4N6fG:2b4jpZ4l1gSCjc4PhfS=>	M4fUVp4yODBizszN		NUnnZm1LTE2VTx?=	M3LvRmlEPTB;MUKwJI5O	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl4NEO0NEc,OjF7NkSzOFA9N2F-
NOMO1	MVPjfZRwfG:6aXPpeJkh[XO\|YYm=	MV;+NVAxKM7:TR?=		MkDTSG1UVw>?	MoTXTWM2OD1zNTDuUS=>	MnLMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
HEL	MkTDZ5l1d3SxeHnjbZR6KGG\|c3H5	MljjglExOCEQvF2=		MX7EUXNQ	M{HHVmlEPTB;MTFOwG0>	MmjUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
K562	NXGySXdr[3m2b4TvfIlkcXS7IHHzd4F6	MUP+NVAxKM7:TR?=		Ml76SG1UVw>?	NYKyUlhVUUN3ME6xNFAh\|ryP	MlzXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7NkSzOFAoRjJzOU[0N\|QxRC:jPh?=
MEG01	M3jY[YN6fG:2b4jpZ4l1gSCjc4PhfS=>	NFLaXWl,OTByIN88US=>		NUPrcXRNTE2VTx?=	NX\rbpZ[UUN3ME2yOUDPxE1?	NY\6WGdmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
HL60	NITCV2hkgXSxdH;4bYNqfHliYYPzZZk>	NF3HUFB,OTByIN88US=>		NUDPTWdMTE2VTx?=	MkTtTWM2OD16OUCgcm0>	NX\SOmYxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
MV4;11	MVfBdI9xfG:\|aYOgZZN{[Xl?	NIfkbGt,OTByIN88US=>		NX60UWZUTE2VTx?=	Mo\GbY5lfWOnczDhdI9xfG:\|aYO=	NXfxd\|h6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
MOLM13	NHjNN2pCeG:ydH;zbZMh[XO\|YYm=	NF;yXWF,OTByIN88US=>		M4\6RWROW09?	MnLjbY5lfWOnczDhdI9xfG:\|aYO=	NXzaWppPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5OlQ{PDBpPkKxPVY1OzRyPD;hQi=>
MV4;11	MYDGeY5kfGmxbjDhd5NigQ>?			M2OxZmROW09?	NGXVe2pl\WO{ZXHz[ZMhfGinIILlZ5J2cXSvZX70JI9nKEKUREOvOEBidmRiaX3wZYlz\WRicnXjdpVqfG2nboSgc4YhS0SNOTDhcoQhWEGIMTD0c{B1cGVidILhcpNkemmydHnvcoFtKHO2YYL0JJNqfGV?	M{HrZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOU[0N\|QxLz5{MUm2OFM1ODxxYU6=
PBMC	MnHFSpVv[3Srb36gZZN{[Xl?			MoHNSG1UVw>?	M3nBb4lvcGmkaYTzJGlNNTZid3n0bEBxUUN3MDDv[kA3Njd?	NW\xfY5CRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0N\|cyOTVpPkKyOFM4OTF3PD;hQi=>
A2	NHzGXmFHfW6ldHnvckBie3OjeR?=	M4rrfp4yOCEQvF2=		MnXpSG1UVw>?	M4jpS5Jm[WO2aY\heIV{KGyjdHXueEBJUVZvMR?=	Ml;QQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{NUWyNVgoRjJ\|MkW1NlE5RC:jPh?=
A72	MX7GeY5kfGmxbjDhd5NigQ>?	MVT+NVAh\|ryP		MmDWSG1UVw>?	NGO2bmRz\WGldHn2ZZRmeyCuYYTlcpQhUEmYLUG=	M2\Gd\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MkW1NlE5Lz5{M{K1OVIyQDxxYU6=
BC1	MkDtS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MV\+NUDPxE1?		NEnOSXVFVVOR	NH\FenpKSzVyPUKyNEBvVQ>?	M1zifVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
BC3	MXfHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?	NUTLRpJyhjFizszN		NFLrbmdFVVOR	MlP2TWM2OD12NkCgcm0>	NXjUW3J7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
BCBL1	M{ftWWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	MWT+NUDPxE1?		NWrr[mNZTE2VTx?=	NVm3V2V4UUN3ME2zN\|Ahdk1?	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
BJAB	NV:zfZRMT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	MkWwglEh\|ryP		M{nNR2ROW09?	M1Lrd2lEPTB;OUewJI5O	NFvabWU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
Namalwa	NX[wVXJmT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	NETwT5J,OSEQvF2=		MVPEUXNQ	Mn\BTWM2OD17N{Cgcm0>	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
Jurkat	NEnrXXhIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	MV\+NUDPxE1?		MYXEUXNQ	M3jId2lEPTB;MUKyNEBvVQ>?	NHr2fZo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
MM1S	NWrkRWEzT3Kxd4ToJIlvcGmkaYTvdpkh[XO\|YYm=	Mo\PglEh\|ryP		NX3WTnpmTE2VTx?=	MoXITWM2OD15NkCgcm0>	NEDIbFY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
U266	MoPoS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	MnmxglEh\|ryP		M3XPcmROW09?	NFr6O\|JKSzVyPUm1NEBvVQ>?	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd7MkS0PEc,OjN5OUK0OFg9N2F-
UM-PEL-1	M2fIeWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M1H0XZ4yKM7:TR?=		M2nhOmROW09?	M2ezOWlEPTB;MkGwJI5O	NUL5SnFpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
UM-PEL-3	M2jMfmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	M2ribJ4yKM7:TR?=		MmH1SG1UVw>?	M4LZT2lEPTB;MUiwJI5O	NInzN3I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BC1	NX[yZVZUTnWwY4Tpc44h[XO\|YYm=	MnnZOVAxKG6P		M13admROW09?	MUTpcoR2[2W\|IHPlcIwu[3mlbHWgZZJz\XO2	NYXPbnRbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3PVI1PDhpPkKzO\|kzPDR6PD;hQi=>
BC3	M2HBW2Z2dmO2aX;uJIF{e2G7	NF2xZ3E2ODBibl2=		NVywWYR{TE2VTx?=	MXzpcoR2[2W\|IHPlcIwu[3mlbHWgZZJz\XO2	NFTte3g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BC1	M3HBZmZ2dmO2aX;uJIF{e2G7	M2Xkb\|gxOCCwTR?=		MkH3SG1UVw>?	NHvIZmRz\WS3Y3XzJIMuVXmlIIDyc5RmcW5ibHX2[Yx{	NHjLNJA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e5NlQ1QCd-MkO3PVI1PDh:L3G+
BC3	M4D4W2Z2dmO2aX;uJIF{e2G7	M1;aTFgxOCCwTR?=		Mn;rSG1UVw>?	NX64WYpyemWmdXPld{BkNU27YzDwdo91\WmwIHzleoVtew>?	M4jRSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|N{myOFQ5Lz5{M{e5NlQ1QDxxYU6=
H929	MWfGeY5kfGmxbjDhd5NigQ>?	MYj+NUDPxE1?		MmfVSG1UVw>?	MWLpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	M2TOTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
KMS12PE	NVTUSGhVTnWwY4Tpc44h[XO\|YYm=	NWTtbWZphjFizszN		MknPSG1UVw>?	NIjLUY9qdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS12BM	MU\GeY5kfGmxbjDhd5NigQ>?	MlX5glEh\|ryP		MmfESG1UVw>?	MUHpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
KMS18	NWLndIJ1TnWwY4Tpc44h[XO\|YYm=	NULVRWN{hjFizszN		NUnKd3dRTE2VTx?=	Mor3bY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	NX\ST\|RrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS11	M{LMPGZ2dmO2aX;uJIF{e2G7	NV7keWM1hjFizszN		MoXVSG1UVw>?	M1y3cYlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S=	M1m0XlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O1OFk6Lz5{NEOzOVQ6QTxxYU6=
RPMI8226	MWHGeY5kfGmxbjDhd5NigQ>?	NYH3SoROhjFizszN		NGPs[oFFVVOR	MojZbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	NV;VboRFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
H929	MV3BdI9xfG:\|aYOgZZN{[Xl?	NEHIOld,OSEQvF2=		NV7JZ\|V6TE2VTx?=	Mkn3bY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?	NXjhXGVoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzN\|U1QTlpPkK0N\|M2PDl7PD;hQi=>
KMS12PE	NH;tZWtCeG:ydH;zbZMh[XO\|YYm=	MVL+NUDPxE1?		NEm5SldFVVOR	NVO5bmt4cW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	Moi1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
KMS12BM	M{m1e2Fxd3C2b4Ppd{Bie3OjeR?=	M1P5eZ4yKM7:TR?=		NVLTc2R5TE2VTx?=	MkeybY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?	NGD5UpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS18	M160UGFxd3C2b4Ppd{Bie3OjeR?=	MXX+NUDPxE1?		NG[1WZVFVVOR	MYnpcoR2[2W\|IHPlcIwh[XCxcITvd4l{	NH3NPWM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEOzOVQ6QSd-MkSzN\|U1QTl:L3G+
KMS11	M4XkVGFxd3C2b4Ppd{Bie3OjeR?=	NV7tUpBQhjFizszN		MkDqSG1UVw>?	MUfpcoR2[2W\|IHPlcIwh[XCxcITvd4l{	MmLMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{W0PVkoRjJ2M{O1OFk6RC:jPh?=
RPMI8226	MU\BdI9xfG:\|aYOgZZN{[Xl?	NHLSU21,OSEQvF2=		MkT2SG1UVw>?	MV3pcoR2[2W\|IHPlcIwh[XCxcITvd4l{	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDN\|NUS5PUc,OjR\|M{W0PVk9N2F-
U87MG	NGrzNG5HfW6ldHnvckBie3OjeR?=	MWT+NVAh\|ryP		NWixfWQyTE2VTx?=	MXjy[YR2[2W\|IGW4O21IKGOnbHz1cIFzKEGWUDD3bZRpKEmFNUCgc4YhOS5yNTFOwG0>	MlHVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2OU[zPFEoRjJ2NEm2N\|gyRC:jPh?=
A172	M3rHXmZ2dmO2aX;uJIF{e2G7	MnzHglExKM7:TR?=		M33TO2ROW09?	MWny[YR2[2W\|IHPlcIx2dGG{IFHUVEB4cXSqIFnDOVAhd2ZiMT6yPEDPxE1?	NVTkUm5wRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVY{QDFpPkK0OFk3OzhzPD;hQi=>
SW1783	NU\TbIRrTnWwY4Tpc44h[XO\|YYm=	M1XBTJ4yOCEQvF2=		NVnUeXhKTE2VTx?=	NUXISWFNemWmdXPld{Bk\WyudXzhdkBCXFBid3n0bEBKSzVyIH;mJFIvPjhizszN	NVrQfFZVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0PVY{QDFpPkK0OFk3OzhzPD;hQi=>
U87MG	NXfqXndnTnWwY4Tpc44h[XO\|YYm=	NESwcFl,OTBizszN		NX;GfXNxTE2VTx?=	M3jxc4lv[3KnYYPld{Bxem:yb4L0bY9vKG:oIHPlcIx{KGmwIITo[UBIOS:VIITyZY5{cXSrb36=	NHXaPWw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES5OlM5OSd-MkS0PVY{QDF:L3G+
RAW267.4	MlHDSpVv[3Srb36gZZN{[Xl?	M1r0UVEh\|ryP		MnTMSG1UVw>?	MULy[YR2[2W\|IFnMMVYheHKxZIXjeIlwdiCrbnT1Z4VlKGK7IFzQVy=>	M3:3cVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEW5NFA5Lz5{NEi1PVAxQDxxYU6=
RAW267.4	NH;lV5NHfW6ldHnvckBie3OjeR?=	NX\rVVFXOSEQvF2=		M{HUfmROW09?	NW\tN2hOemWmdXPld{B1cGViYYPzc4Nq[XSrb36gZoV1f2WnbjDCVmQ1KGGwZDDhZ4V1gWyjdHXkJJA3PQ>?	Mo\vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR6NUmwNFgoRjJ2OEW5NFA5RC:jPh?=
Me007	MkDkS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	NV;jeIZFhjFyMDFOwG0>		NHjmOlNFVVOR	MmLnbY5pcWKrdIOgeIhmKGe{b4f0bC=>	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
SK-Mel-28	NHu1cHpIem:5dHigbY5pcWKrdH;yfUBie3OjeR?=	NVz0TJM{hjFyMDFOwG0>		MX\EUXNQ	MUXpcohq[mm2czD0bIUh\3Kxd4To	NETHWXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RMU	Mn7PS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M37pOp4yODBizszN		NE\XTmlFVVOR	NF3kNItqdmirYnn0d{B1cGViZ4Lve5Rp	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-JD	MnnTS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?	M2X6UZ4yODBizszN		MlHSSG1UVw>?	MkXQbY5pcWKrdIOgeIhmKGe{b4f0bC=>	M33kV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RM	M3O0Zmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7	NGHrfYp,OTByIN88US=>		MmDrSG1UVw>?	MVXpcohq[mm2czD0bIUh\3Kxd4To	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Me007	MXHBdI9xfG:\|aYOgZZN{[Xl?	MUP+NVAxKM7:TR?=		Mkm1SG1UVw>?	M{nUfolv\HWlZYOgZZBweHSxc3nz	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
SK-Mel-28	NIT1e3pCeG:ydH;zbZMh[XO\|YYm=	M{nK[Z4yODBizszN		NH7PNJRFVVOR	M3j1dIlv\HWlZYOgZZBweHSxc3nz	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-RMU	M3y2RWFxd3C2b4Ppd{Bie3OjeR?=	MYT+NVAxKM7:TR?=		NEHTTXdFVVOR	MoX0bY5lfWOnczDhdI9xfG:\|aYO=	NGi0[pU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-JD	NIX1d2xCeG:ydH;zbZMh[XO\|YYm=	NGXJO3V,OTByIN88US=>		NWq5bVM3TE2VTx?=	NHnsfIZqdmS3Y3XzJIFxd3C2b4Ppdy=>	NHHWWWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
Mel-RM	M3riTmFxd3C2b4Ppd{Bie3OjeR?=	MlL2glExOCEQvF2=		MlzpSG1UVw>?	NGTTRlZqdmS3Y3XzJIFxd3C2b4Ppdy=>	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Me007	NGjNd2hHfW6ldHnvckBie3OjeR?=	MofZNVAh\|ryP		NYrJ[HU5TE2VTx?=	M17mZYlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgZpkhfXC{ZXf1cIF1cW:wIH;mJJAzOQ>?	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
SK-Mel-28	NXTQTVcyTnWwY4Tpc44h[XO\|YYm=	MmHqNVAh\|ryP		M130NWROW09?	NVnRNI5YcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBjgSC3cILl[5Vt[XSrb36gc4YheDJz	NVG3PFNWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RMU	M1KwS2Z2dmO2aX;uJIF{e2G7	M4LLPVExKM7:TR?=		NV7oeXBUTE2VTx?=	NYOwUVczcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeEBjgSC3cILl[5Vt[XSrb36gc4YheDJz	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Mel-JD	NYexXYhHTnWwY4Tpc44h[XO\|YYm=	M1HNe\|ExKM7:TR?=		MlTISG1UVw>?	MXnpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2IHL5JJVxemWpdXzheIlwdiCxZjDwNlE>	Mm[4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7ME[xN\|coRjJ2OUC2NVM4RC:jPh?=
Mel-RM	NGPVXYJHfW6ldHnvckBie3OjeR?=	Mmf5NVAh\|ryP		MlriSG1UVw>?	MnTtbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dDDifUB2eHKnZ4XsZZRqd25ib3[gdFIy	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyNkGzO{c,OjR7ME[xN\|c9N2F-
Me007	MXPGeY5kfGmxbjDhd5NigQ>?	NUTvcmNOOTBizszN		M2Ppb2ROW09?	MXj1dJJm\3WuYYTld{Bxem:jcH;weI91cWNiYX7kJINmdGxiY4njcIUh[XK{ZYP0JIdmdmW\|	NIG2dXU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
SK-Mel-28	M2jjV2Z2dmO2aX;uJIF{e2G7	NX;hbG94OTBizszN		Ml;TSG1UVw>?	NIjLXpB2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	M{K3blxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-RMU	MVPGeY5kfGmxbjDhd5NigQ>?	NXrxOJZlOTBizszN		NHvJ[JNFVVOR	NEDSWph2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	M1XOSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUC2NVM4Lz5{NEmwOlE{PzxxYU6=
Mel-JD	MVvGeY5kfGmxbjDhd5NigQ>?	Mn7uNVAh\|ryP		M3;OSmROW09?	NIfSVoN2eHKnZ4XsZZRmeyCycn;hdI9xfG:2aXOgZY5lKGOnbHygZ5lkdGViYYLy[ZN1KGenbnXz	NVPmWpNsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFYyOzdpPkK0PVA3OTN5PD;hQi=>
Mel-RM	MXnGeY5kfGmxbjDhd5NigQ>?	MXWxNEDPxE1?		M2fVUWROW09?	M2r6e5VxemWpdXzheIV{KHC{b3Hwc5B1d3SrYzDhcoQh[2WubDDjfYNt\SCjcoLld5Qh\2WwZYO=	NGDjO249[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwOlE{Pyd-MkS5NFYyOzd:L3G+
HepG2	NWXSOYF5TnWwY4Tpc44h[XO\|YYm=		NGfvR\|IyQCCqcoO=		MWfVdJJm\3WuYYTpc44hd2ZiQYDvRVEh\XiycnXzd4lwdiCrbjDoeY1idiCKZYDHNkBk\WyuczDhd5Nme3OnZDDhd{Bkd26lZX70doF1cW:wIILldZVqemWmIITvJIlv[3KnYYPlJFcxLSCxZjDseYNq\mW{YYPlJIFkfGm4aYT5JIFnfGW{IEG4JIhzeyCkeTDseYNq\mW{YYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEWFMUewJF0hOC5yOTFOwG0v	NGr1eVE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO4OlUzQSd-MkKzPFY2Ojl:L3G+
Raji	M1XWbGZ2dmO2aX;uJIF{e2G7		MmLnOEBpenN?		MoPNTY5pcWKrdHnvckBw\iCEUlS0JIlvKGi3bXHuJHJicmliY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIH;mJG1[SyCneIDy[ZN{cW:wIHHmeIVzKDRiaILzMEBKSzVyIE2gNE4yOyEQvF2u	MorkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC3OVgoRjJ2OUCwO\|U5RC:jPh?=
MV4-11	MmXtS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		M3fJV\|czKGi{cx?=		NXrxWIs1T3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hVVZ2LUGxJINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCVUlKgZZN{[XluIFnDOVAhRSByLkGxPUDPxE1w	NYrLbY14RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1OVk1OjhpPkK1OVU6PDJ6PD;hQi=>
MM1S	MVfHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		Mn3kO\|IhcHK\|		Mn33S5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gUW0yWyClZXzsd{Bi\nSncjC3NkBpenNiYomgV3JDKGG\|c3H5MEBKSzVyIE2gNE4zQTlizszNMi=>	MlXEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV3NUm0NlgoRjJ3NUW5OFI5RC:jPh?=
HT-29	MmnuS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		NX3xT4tmPzJiaILz		NXrEUJVyT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hUFRvMkmgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiSVO1NEA:KDBwOUS1JO69VS5?	M{XvfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NUW5OFI5Lz5{NUW1PVQzQDxxYU6=
Rosetta2 DE3	NXK5SnE2TnWwY4Tpc44h[XO\|YYm=		M{eyTlMxKG2rboO=		NFH4d2RFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEOEBDTDFiKES0JJRwKDF4ODDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBKSzVyIE2gNE4xOzF5IN88UU4>	NGTxV2I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
MV4-11	M1fCPGN6fG:2b4jpZ4l1gSCjc4PhfS=>		MVG0JIRigXN?		MXPDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNWlQuOTFiY3XscJMhcGG{Yn;ybY5oKE2OTEGg[pV{cW:wIHflcoUh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhPCCmYYnzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[XO\|YYmsJGlEPTBiPTCwMlE3OiEQvF2u	NFXJR2Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	M1HUUWZ2dmO2aX;uJIF{e2G7		M4fIZ\|MxKG2rboO=		Mn7zSIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKURESgRmQzKCh\|M{OgeI8hPDZyIHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGlEPTBiPTCwMlIzPiEQvF2u	NVLrN3prRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
MOLM13	M3j2T2N6fG:2b4jpZ4l1gSCjc4PhfS=>		M1LSW\|Qh\GG7cx?=		NXHkU2xqS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVU:OTUGzJINmdGy\|IHjhdoJwemmwZzDNUGwyKG[3c3nvckBo\W6nIHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IESg[IF6eyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHHzd4F6NCCLQ{WwJF0hOC5{Mkig{txONg>?	Ml7VQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	MliwSpVv[3Srb36gZZN{[Xl?		NW\o[YI4OzBibXnudy=>		NY[wbnBRUW6qaXLpeIlwdiCxZjDGRW0udGGkZXzl[EBbSkF{NEigZolv\GmwZzD0c{Bz\WOxbXLpcoFvfCCqdX3hckBPNXSncn3pcoFtKEirc{[teIFo\2WmIFLSSFQh[nKxbX;kc41icW5iMTCoOFQhfG9iMU[4JJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvODNzNzFOwG0v	NWPRcXhrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
MV4-11	MnHkS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		MUK0JIRigXN?		M2rnc2dzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJG1XPC1zMTDj[YxteyCjZoTldkA1KGSjeYOgZpkhX1OWLUigZZN{[XluIFnDOVAhRSByLkG2NkDPxE1w	NXPkO5Z5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
Rosetta2 DE3	NULhPWw2TnWwY4Tpc44h[XO\|YYm=		M1\FNFMxKG2rboO=		NFXodFNKdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiB{IDizN\|MhfG9iNE[wJJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhUUN3MDC9JFAvOjJ4IN88UU4>	NUH3S2plRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
MOLM13	M2P4fGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NYCz[4ttPCCmYYnz		M2S4UGdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJG1QVE1zMzDj[YxteyCjZoTldkA1KGSjeYOgZpkhX1OWLUigZZN{[XluIFnDOVAhRSByLkKyPEDPxE1w	NXTlOZp[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
Rosetta2 DE3	NHfvOpBHfW6ldHnvckBie3OjeR?=				M{\MXGJqdmSrbnegZYZncW6rdImgeI8h[mmxdHnufYxifGWmIFLSSFMhSkRzIDiyOEB1dyBzNESgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOC5yMkm4JO69VS5?	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	MnTpSpVv[3Srb36gZZN{[Xl?				M4TsbGJqdmSrbnegZYZncW6rdImgeI8h[mmxdHnufYxifGWmIFLSSFMhSkR{IDizNFYhfG9iNEG3JIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDifUBjcW9vbHH5[ZIhcW62ZYLm[ZJwdWW2comgcYV1cG:mLDDL[EA:KDBwMESwOUDPxE1w	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	MnH3SpVv[3Srb36gZZN{[Xl?				MknQRolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQmLEOEBDTDFiKES0JJRwKDF4ODDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYomgZolwNWyjeXXyJIlvfGW{ZnXyc41mfHK7IH3leIhw\CxiS3SgQUAxNjB3Mkig{txONg>?	NVjUOVMzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	MX7GeY5kfGmxbjDhd5NigQ>?				MmrMRolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQmLENkBDTDFiKEeyJJRwKDJyNTDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYomgZolwNWyjeXXyJIlvfGW{ZnXyc41mfHK7IH3leIhw\CxiS3SgQUAxNjB3NEig{txONg>?	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	M3vISGZ2dmO2aX;uJIF{e2G7				NE\ucmpDcW6maX7nJIFn\mmwaYT5JJRwKGKrb4Tpcplt[XSnZDDCVmQzKEKGMjCoN\|Q6KHSxIES2NEBidWmwbzDhZ4llKHKnc3nkeYV{MSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDSc5NmfHSjMjDESVMh[2WubIOgZpkh[mmxLXzhfYVzKGmwdHXy[oVzd22ndIL5JI1mfGixZDygT4QhRSByLkC3NFMh\|ryPLh?=	M2fqdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEiwNFY1Lz5{NkC4NFA3PDxxYU6=
Rosetta2 DE3	MXjGeY5kfGmxbjDhd5NigQ>?				M{PPTWJqdmSrbnegZYZncW6rdImgeI8h[mmxdHnufYxifGWmIFLSSFQhSkR{IDizN\|MhfG9iNE[wJIFucW6xIHHjbYQhemW\|aXT1[ZMqKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGLvd4V1fGF{IFTFN{Bk\WyuczDifUBjcW9vbHH5[ZIhcW62ZYLm[ZJwdWW2comgcYV1cG:mLDDL[EA:KDBwMkG1JO69VS5?	MnW4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyOECwOlQoRjJ4MEiwNFY1RC:jPh?=
Rosetta2 DE3	NE\F[oVHfW6ldHnvckBie3OjeR?=				MlPKRolv\GmwZzDh[oZqdmm2eTD0c{BjcW:2aX75cIF1\WRiQ2LFRmJRKChzMESzJJRwKDFzNUmgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHL5JIJqdy2uYYnldkBqdnSncn\ldo9u\XS{eTDt[ZRpd2RuIFvkJF0hOy5yOESg{txONg>?	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	M3fDO2Z2dmO2aX;uJIF{e2G7		Mn62N\|AhdWmwcx?=		NH\1[VhFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEN{BDTDFiKEK0JJRwKDF2NDDhcYlvdyCjY3nkJJJme2mmdXXzLUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCUb4PleJRiOiCGRUOgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG\|c3H5MEBMcSB;IECuNFA4OiEQvF2u	NUXHN\|F4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	NXHocVhMTnWwY4Tpc44h[XO\|YYm=		NXO3eIZyOzBibXnudy=>		MUnEbZNxdGGlZX3lcpQhd2ZiRlHNMYxi[mWuZXSgXmJCOjR6IH\yc40hSlKGNDDCSFEhMDR2IITvJFE3QCCjbXnuc{Bi[2mmIILld4llfWW\|KTCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDLbUA:KDBwMEC5JO69VS5?	NYjtcYt7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	MVPGeY5kfGmxbjDhd5NigQ>?		NXXDfYpqOzBibXnudy=>		NX;4TJhSTGm\|cHzhZ4Vu\W62IH;mJGZCVS2uYXLlcIVlKFqEQUK0PEBnem:vIFLSSFIhSkRzIDi3NkB1dyB{MEWgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlAxQSEQvF2u	NVfrW4hXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wPFAxPjRpPkK2NFgxODZ2PD;hQi=>
Rosetta2 DE3	M2qyWGZ2dmO2aX;uJIF{e2G7		Mn3ZN\|AhdWmwcx?=		Mlj1SIl{eGyjY3Xt[Y51KG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDmdo9uKEKUREOgRmQzKCh\|ME[geI8hPDF5IHHtbY5wKGGlaXSgdoV{cWS3ZYOpJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKFKxc3X0eIEzKESHMzDj[YxteyCjZoTldkA{OCCvaX7zJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO\|YYmsJGtqKD1iMD6wNlI{KM7:TT6=	NEDmRlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	MlnWSpVv[3Srb36gZZN{[Xl?		MljpN\|AhdWmwcx?=		NFn5e4pFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLENkBDTDJiKEO0PUB1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlA1QTZizszNMi=>	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB6MEC2OEc,OjZyOECwOlQ9N2F-
Rosetta2 DE3	NV[4XXlDTnWwY4Tpc44h[XO\|YYm=		MUizNEBucW6\|		NIXxOYlFcXOybHHj[Y1mdnRib3[gSmFONWyjYnXs[YQhYkKDMkS4JIZzd21iQmLEOEBDTDJiKEOzN{B1dyB2NkCgZY1qdm9iYXPp[EBz\XOrZIXld{khMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlA4PDhizszNMi=>	NIr5UGU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkC4NFA3PCd-Mk[wPFAxPjR:L3G+
Rosetta2 DE3	M{HYUGZ2dmO2aX;uJIF{e2G7		MYmzNEBucW6\|		MUnJcohq[mm2aX;uJI9nKE[DTT3sZYJmdGWmIGrCRVI1QCCkaX7kbY5oKHSxIILlZ49u[mmwYX70JIh2dWGwIF6teIVzdWmwYXygTIl{Pi22YXfn[YQhSlKGNDDido9ud2SxbXHpckAyKCh2NDD0c{AyPjhicnXzbYR2\XNrIHX4dJJme3OnZDDpckBTd3OndIThNkBFTTNiY3XscJMh[W[2ZYKgN\|AhdWmwczDifUBHdG:3cnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7LDDLbUA:KDBwMEC5JO69VS5?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDR4M{S4O{c,Ojh2NkO0PFc9N2F-
Rosetta2 DE3	M{TuVmZ2dmO2aX;uJIF{e2G7		NH6zSpY{OCCvaX7z		NIrFS5dKdmirYnn0bY9vKG:oIF\BUU1t[WKnbHXkJHpDSTJ2ODDibY5lcW6pIITvJJJm[2:vYnnuZY51KGi3bXHuJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRiQmLEOEBjem:vb3TvcYFqdiB{IDizN\|MhfG9iNE[wJJJme2mmdXXzLUBmgHC{ZYPz[YQhcW5iUn;z[ZR1[TJiRFWzJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nliRnzveZJme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfUwhU2liPTCwMlA4PDhizszNMi=>	NYGxRnVZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki0OlM1QDdpPkK4OFY{PDh5PD;hQi=>
THP1	NWDQRYZuSW62aXnu[oxidW2jdH;yfUBie3OjeR?=				Ml;kRY51cWmwZnzhcY1ifG:{eTDhZ5Rqfmm2eTDpckBpfW2jbjDUTHAyKGOnbHzz	NF;LXmI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO4OlUzQSd-MkKzPFY2Ojl:L3G+
HT-29	Mn;4SpVv[3Srb36gZZN{[Xl?	NIHO[lExNjNzMkWgeW0hfG9iNTD1US=>	NHTZTY4zPCCqcoO=		MYrJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gTHQuOjliY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJIMuVXmlIIDyc5RmcW5iZYjwdoV{e2mxbjDheEAxNjNzMkWgeW0hfG9iNTD1UUB2VSCjZoTldkAzPCCqcoOgZpkhX2W\|dHXyckBjdG:2dHnu[{Bu\XSqb3S=	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTV3OUSyPEc,OjV3NUm0Nlg9N2F-
MV4-11	Ml21SpVv[3Srb36gZZN{[Xl?				NEf3NZJKdmirYnn0bY9vKG:oIFLSSFQhcW5iaIXtZY4hVVZ2LUGxJINmdGy\|IHHzd4V{e2WmIHHzJIRwf26{ZXf1cIF1cW:wIH;mJGJEVDJiUl7BJIV5eHKnc4Ppc44h[nliUl7BMZNmeSCjbnHsfZNqew>?	M321UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MkW5O\|UyLz5{OUK1PVc2OTxxYU6=
MV4-11	NFzpVY5HfW6ldHnvckBie3OjeR?=				NV\IfHllUW6qaXLpeIlwdiCxZjDCVmQ1KGmwIHj1cYFvKE2YND2xNUBk\WyuczDhd5Nme3OnZDDhd{Bld3ewcnXneYxifGmxbjDv[kBkVVmFIGLORUBmgHC{ZYPzbY9vKGK7IGLORU1{\XFiYX7hcJl{cXN?	MoTQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl{NUm3OVEoRjJ7MkW5O\|UyRC:jPh?=
U-2 OS	Mkj2dWhVWyCjc4PhfS=>				M{DYVJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCXLUKgU3Mh[2WubIO=	MlzMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
A673	NH3XOYRyUFSVIHHzd4F6				NU\yVVBoeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFG2O\|Mh[2WubIO=	M1zye\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
DAOY	MoPldWhVWyCjc4PhfS=>				NIrmZ2hyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?=	NF7INFM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
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RD	NVnGdm95eUiWUzDhd5NigQ>?				Mn3CdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKGIHPlcIx{	NIi5V5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-SH	NH\yWoNyUFSVIHHzd4F6				MXvxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3TTEBk\Wyucx?=	NVvGV253RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-12	MUjxTHRUKGG\|c3H5				M4W0e5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2xNkBk\Wyucx?=	NWD2U45nRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	NVvvPFZ7eUiWUzDhd5NigQ>?				Mo\PdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy\|	MoLqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB1643	MUjxTHRUKGG\|c3H5				NWnEZ5N7eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=>	MkjaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
OHS-50	Mnn0dWhVWyCjc4PhfS=>				NX7ReVVSeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	NIjaZYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
fibroblast cells	MlnidWhVWyCjc4PhfS=>				MWfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5Ih[2:wdILvcEBJcCC5aXzkJJR6eGViZnnido9jdGG\|dDDj[Yxtew>?	NHzKTlU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh41	MlPBdWhVWyCjc4PhfS=>				NXzs[IJbeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoOFEh[2WubIO=	MlW5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh30	MWTxTHRUKGG\|c3H5				MoDkdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqM{CgZ4VtdHN?	M3HFVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SJ-GBM2	MkXldWhVWyCjc4PhfS=>				NUWxOHNweUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM>	NHvEc3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	NGPyUWJyUFSVIHHzd4F6				M4nUbJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz	NECy[XE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	NIWyd5FyUFSVIHHzd4F6				MnP5dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6ELVXCZ\|Eh[2WubIO=	M3rFe\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	MXzxTHRUKGG\|c3H5				NYjaXpFFeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz	NX2xNWlRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18	MX3xTHRUKGG\|c3H5				Mn;IdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqMUigZ4VtdHN?	NGGxdYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	α-SMA / Fibronectin / Collagen-1; PubMed: 27732564 Oncotarget Normally cultured NRK-49F cells were treated with I-BET151 (0-5μM) for 36 h. Then, cell lysates were prepared and subjected to immunoblot analysis with antibodies against α-SMA, collagen-1, fibronectin, and GAPDH. FoxM1 / AURKB / Survivin / cyclin B / PLK1; PubMed: 26877780 Theranostics OVTOKO and OVCA420 cells were treated with DMSO, JQ1 (1 μM) or I-BET151 (1 μM). Cell lysates were immunoblotted with indicated antibodies. HP1α / HP1β / HP1γ; PubMed: 30386240 Front Pharmacol Protein expression levels of HP1α, β, and γ in U937, R-U937, HL-60, and R-HL-60 cells after incubation with I-BET151 at indicated dose for 48 h. Typical blots from a representative experiment are shown. The experiments were repeated three times.	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

Kinase Assay: ^[1]	- Collapse 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]	- Collapse 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]	- Collapse 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 Download I-BET151 (GSK1210151A) SDF

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

In vivo Formulation Calculator (Clear solution)

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

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% DMSO+ % + % Tween 80+ % ddH₂O

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Working concentration： mg/ml；

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

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

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

Bio Calculators

Molarity Calculator

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

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The Serial Dilution Calculator Equation

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Computed Result

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Molecular Weight Calculator

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

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Epigenetic Reader Domain Signaling Pathway Map

Epigenetic Reader Domain Inhibitors with Unique Features

Selective BET Inhibitor

PFI-1 (PF-6405761) : BRD4-selective, IC50=0.22 μM.
Most Potent BET Inhibitor

I-BET-762 : BET proteins, IC50=~35 nM.
BET Inhibitor in Clinical Trial

RVX-208 ^New : Phase II for Dyslipidemia.

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I-BET151 (GSK1210151A)